bioRxiv Channel: Impact of Genomic Variation on Function (IGVF)
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This feed contains articles for bioRxiv Channel "Impact of Genomic Variation on Function (IGVF)"
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EUGENe: A Python toolkit for predictive analyses of regulatory sequences
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https://biorxiv.org/cgi/content/short/2022.10.24.513593v1?rss=1"
Klie, A.Stites, H.Jores, T.Carter, H.2022-10-26doi:10.1101/2022.10.24.513593Cold Spring Harbor Laboratory Press2022-10-26
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A framework for summarizing chromatin state annotations within and identifying differential annotations across groups of samples
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https://biorxiv.org/cgi/content/short/2022.05.08.491094v1?rss=1"
Vu, H. T.Koch, Z.Fiziev, P.Ernst, J.2022-05-08doi:10.1101/2022.05.08.491094Cold Spring Harbor Laboratory Press2022-05-08
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Chromatin state modeling across individuals reveals global patterns of histone modifications
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https://biorxiv.org/cgi/content/short/2022.08.02.502571v1?rss=1"
Zou, J.Ernst, J.2022-08-03doi:10.1101/2022.08.02.502571Cold Spring Harbor Laboratory Press2022-08-03
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Exploring genomic data coupled with 3D chromatin structures using the WashU Epigenome Browser
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https://biorxiv.org/cgi/content/short/2022.01.18.476849v1?rss=1"
Li, D.Purushotham, D.Harrison, J. K.Wang, T.2022-01-21doi:10.1101/2022.01.18.476849Cold Spring Harbor Laboratory Press2022-01-21
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ChromGene: Gene-Based Modeling of Epigenomic Data
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https://biorxiv.org/cgi/content/short/2022.05.24.493345v1?rss=1"
Jaroszewicz, A.Ernst, J.2022-05-25doi:10.1101/2022.05.24.493345Cold Spring Harbor Laboratory Press2022-05-25
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Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2
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https://biorxiv.org/cgi/content/short/2022.05.02.490368v1?rss=1"
Schmidt, H.Zhang, M.Mourelatos, H.Sanchez-Rivera, F. J.Lowe, S. W.Ventura, A.Leslie, C. S.Pritykin, Y.2022-05-03doi:10.1101/2022.05.02.490368Cold Spring Harbor Laboratory Press2022-05-03
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Heterogeneity of Inflammation-associated Synovial Fibroblasts in Rheumatoid Arthritis and Its Drivers
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https://biorxiv.org/cgi/content/short/2022.02.28.482131v1?rss=1"
Smith, M. H.Gao, V. R.Schizas, M.Kochen, A.DiCarlo, E.Goodman, S.Norman, T. M.Donlin, L.Leslie, C. S.Rudensky, A. Y.2022-03-02doi:10.1101/2022.02.28.482131Cold Spring Harbor Laboratory Press2022-03-02
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Diverse digital and fuzzy composite transcriptional elements are prevalent features of mammalian cis-regulomes
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https://biorxiv.org/cgi/content/short/2021.11.26.470154v1?rss=1"
20,000 CEs in open chromatin regions of diverse immune cells and validated many using CAP-SELEX, ChIP-Seq and STARR-seq datasets. Strikingly, the CEs manifested a bimodal distribution of configurations, termed digital and fuzzy, based on their stringent or relaxed stereospecific constraints, respectively. Digital CEs mediate cooperative as well as anti-cooperative binding of structurally diverse TFs that likely reflect AND/OR genomic logic gates. In contrast, fuzzy CEs encompass a less diverse set of TF motif pairs that are selectively enriched in p300 associated, multi-genic enhancers. The annotated CEs greatly expand the regulatory DNA motif lexicon and the universe of TF-TF interactions that underlie combinatorial logic of gene regulation.
]]>Chaudhri, V. K.Singh, H.2021-11-27doi:10.1101/2021.11.26.470154Cold Spring Harbor Laboratory Press2021-11-27
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Evolution of transposable element-derived enhancer activity
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https://biorxiv.org/cgi/content/short/2022.03.16.483999v1?rss=1"
Du, A. Y.Zhuo, X.Sundaram, V.Jensen, N. O.Chaudhari, H. G.Saccone, N. L.Cohen, B. A.Wang, T.2022-03-17doi:10.1101/2022.03.16.483999Cold Spring Harbor Laboratory Press2022-03-17
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The dynseq genome browser track enables visualization of context-specific, dynamic DNA sequence features at single nucleotide resolution
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https://biorxiv.org/cgi/content/short/2022.05.26.493621v1?rss=1"
Nair, S.Barrett, A.Li, D.Raney, B. J.Lee, B. T.Kerpedjiev, P.Ramalingam, V.Pampari, A.Lekschas, F.Wang, T.Haeussler, M.Kundaje, A.2022-05-28doi:10.1101/2022.05.26.493621Cold Spring Harbor Laboratory Press2022-05-28
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A mutation rate model at the basepair resolution identifies the mutagenic effect of Polymerase III transcription
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https://biorxiv.org/cgi/content/short/2022.08.20.504670v1?rss=1"
Seplyarskiy, V.Lee, D. J.Koch, E. M.Lichtman, J. S.Luan, H. H.Sunyaev, S. R.2022-08-21doi:10.1101/2022.08.20.504670Cold Spring Harbor Laboratory Press2022-08-21
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FAVOR: Functional Annotation of Variants Online Resource and Annotator for Variation across the Human Genome
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https://biorxiv.org/cgi/content/short/2022.08.28.505582v1?rss=1"
Zhou, H.Arapoglou, T.Li, X.Li, Z.Zheng, X.Moore, J. E.Asok, A.Kumar, S.Blue, E. E.Buyske, S.Cox, N.Felsenfeld, A.Gerstein, M.Kenny, E.Li, B.Matise, T.Philippakis, A.Rehm, H.Sofia, H. J.Neale, B.Snyder, G.Weng, Z.Sunyaev, S.Lin, X.2022-08-29doi:10.1101/2022.08.28.505582Cold Spring Harbor Laboratory Press2022-08-29
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Optimizing and benchmarking polygenic risk scores with GWAS summary statistics
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https://biorxiv.org/cgi/content/short/2022.10.26.513833v1?rss=1"
Zhao, Z.Gruenloh, T.Wu, Y.Sun, Z.Miao, J.Wu, Y.Song, J.Lu, Q.2022-10-27doi:10.1101/2022.10.26.513833Cold Spring Harbor Laboratory Press2022-10-27
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Mutagenesis at non-B DNA motifs in the human genome: a course correction
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https://biorxiv.org/cgi/content/short/2022.02.08.479604v1?rss=1"
McGinty, R. J.Sunyaev, S. R.2022-02-09doi:10.1101/2022.02.08.479604Cold Spring Harbor Laboratory Press2022-02-09
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PerturbNet predicts single-cell responses to unseen chemical and genetic perturbations
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https://biorxiv.org/cgi/content/short/2022.07.20.500854v1?rss=1"
Yu, H.Welch, J. D.2022-07-21doi:10.1101/2022.07.20.500854Cold Spring Harbor Laboratory Press2022-07-21
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Cross-tissue eQTL mapping in the presence of missing data via surrogate outcome analysis
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https://biorxiv.org/cgi/content/short/2020.11.29.403063v1?rss=1"
McCaw, Z. R.Gaynor, S. M.Sun, R.Lin, X.2020-11-30doi:10.1101/2020.11.29.403063Cold Spring Harbor Laboratory Press2020-11-30
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Modeling tissue co-regulation to estimate tissue-specific contributions to disease
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https://biorxiv.org/cgi/content/short/2022.08.25.505354v1?rss=1"
Amariuta, T.Siewert-Rocks, K.Price, A. L.2022-08-26doi:10.1101/2022.08.25.505354Cold Spring Harbor Laboratory Press2022-08-26
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A statistical genetics guide to identifying HLA alleles driving complex disease
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https://biorxiv.org/cgi/content/short/2022.08.24.504550v1?rss=1"
Sakaue, S.Gurajala, S.Curtis, M.Luo, Y.Choi, W.Ishigaki, K.Kang, J. B.Rumker, L.Deutsch, A. J.Schonherr, S.Forer, L.LeFaive, J.Fuchsberger, C.Han, B.Lenz, T. L.de Bakker, P. I. W.Smith, A. V.Raychaudhuri, S.2022-08-26doi:10.1101/2022.08.24.504550Cold Spring Harbor Laboratory Press2022-08-26
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Evidence-based calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for clinical use of PP3/BP4 criteria
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https://biorxiv.org/cgi/content/short/2022.03.17.484479v1?rss=1"
Pejaver, V.Byrne, A. B.Feng, B.-J.Pagel, K. A.Mooney, S. D.Karchin, R.O'Donnell-Luria, A.Harrison, S. M.Tavtigian, S. V.Greenblatt, M. S.Biesecker, L. G.Radivojac, P.Brenner, S. E.ClinGen Sequence Variant Interpretation Working Group,2022-03-19doi:10.1101/2022.03.17.484479Cold Spring Harbor Laboratory Press2022-03-19
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Enrichment of somatic mutations in schizophrenia brain targets prenatally active transcription factor bindings sites
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https://biorxiv.org/cgi/content/short/2022.02.23.481681v1?rss=1"
15% increase in genome-wide sSNV compared to controls (p < 2e-10). Remarkably, mosaic T>G mutations and CpG transversions (CpG>GpG or CpG>ApG) were 79- and 62-fold enriched, respectively, at transcription factor binding sites (TFBS) in SCZ, but not in controls. The pattern of T>G mutations resembles mutational processes in cancer attributed to oxidative damage that is sterically blocked from DNA repair by transcription factors (TFs) bound to damaged DNA. The CpG transversions similarly suggest unfinished DNA demethylation resulting in abasic sites that can also be blocked from repair by bound TFs. Allele frequency analysis suggests that both localized mutational spikes occur in the first trimester. We call this prenatal mutational process "skiagenesis" (from the Greek skia, meaning shadow), as these mutations occur in the shadow of bound TFs. Skiagenesis reflects as-yet unidentified prenatal factors and is associated with SCZ risk in a subset ([~]13%) of cases. In turn, mutational disruption of key TFBS active in fetal brain is well positioned to create SCZ-specific gene dysregulation in concert with germline risk genes. Skiagenesis provides a fingerprint for exploring how epigenomic regulation and prenatal factors such as maternal infection or immune activation may shape the developmental mutational landscape of human brain.
]]>Maury, E. A.Jones, A.Seplyarskiy, V.Rosenbluh, C.Bae, T.Wang, Y.Abyzov, A.Khoshkoo, S.Chahine, Y.Brain Somatic Mosaicism Network,Park, P. J.Akbarian, S.Lee, E. A.Sunyaev, S. R.Walsh, C. A.Chess, A.2022-02-24doi:10.1101/2022.02.23.481681Cold Spring Harbor Laboratory Press2022-02-24
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Deciphering the Impact of Genetic Variation on Human Polyadenylation
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https://biorxiv.org/cgi/content/short/2022.05.09.491198v1?rss=1"
44 million variants against gnomAD. While loss-of-function variants were generally selected against, we also find specific clinical conditions linked to gain-of-function mutations. For example, using APARENT2s predictions we detect an association between gain-of-function mutations in the 3-end and Autism Spectrum Disorder.
]]>Linder, J.Kundaje, A.Seelig, G.2022-05-10doi:10.1101/2022.05.09.491198Cold Spring Harbor Laboratory Press2022-05-10
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Limited overlap of eQTLs and GWAS hits due to systematic differences in discovery
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https://biorxiv.org/cgi/content/short/2022.05.07.491045v1?rss=1"
Mostafavi, H.Spence, J. P.Naqvi, S.Pritchard, J. K.2022-05-08doi:10.1101/2022.05.07.491045Cold Spring Harbor Laboratory Press2022-05-08
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Recurrent mutation in the ancestry of a rare variant
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https://biorxiv.org/cgi/content/short/2022.08.18.504427v1?rss=1"
Wakeley, J.Fan, W. T.Koch, E.Sunyaev, S.2022-08-18doi:10.1101/2022.08.18.504427Cold Spring Harbor Laboratory Press2022-08-18
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A unique epigenomic landscape defines CD8+ tissue-resident memory T cells
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https://biorxiv.org/cgi/content/short/2022.05.04.490680v1?rss=1"
View larger version (56K):
org.highwire.dtl.DTLVardef@b03f1corg.highwire.dtl.DTLVardef@ff6871org.highwire.dtl.DTLVardef@220db2org.highwire.dtl.DTLVardef@1b15166_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIscATAC atlas reveals the epigenetic variance of memory CD8+ T cell subsets over the course of acute infection
C_LIO_LIEarly bifurcation of memory precursors leads to circulating versus tissue-resident cell fates
C_LIO_LIIntegrating transcriptional and epigenetic analyses identified organ-specific TRM cell regulators including HIC1 and BACH2
C_LIO_LIEpigenetic distinction of TRM cells and TEX cell subsets
C_LI
]]>Buquicchio, F. A.Fonseca, R.Belk, J. A.Evrard, M.Obers, A.Qi, Y.Daniel, B.Yost, K. E.Satpathy, A. T.Mackay, L. K.2022-05-06doi:10.1101/2022.05.04.490680Cold Spring Harbor Laboratory Press2022-05-06
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Antigen presentation by type 3 innate lymphoid cells instructs the differentiation of gut microbiota-specific regulatory T cells
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https://biorxiv.org/cgi/content/short/2021.11.19.469318v1?rss=1"
Kedmi, R.Najar, T.Mesa, K. R.Grayson, A.Kroehling, L.Hao, Y.Hao, S.Pokrovskii, M.Xu, M.Talbot, J.Wang, J.Anderson, M. S.Gardner, J. M.Laufer, T. M.Aifantis, I.Bartleson, J. M.Allen, P. M.Stoeckius, M.Littman, D. R.2021-11-20doi:10.1101/2021.11.19.469318Cold Spring Harbor Laboratory Press2021-11-20
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Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence
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https://biorxiv.org/cgi/content/short/2022.04.20.488974v1?rss=1"
Belk, J.Yao, W.Ly, N.Freitas, K.Chen, Y.-T.Shi, Q.Valencia, A.Shifrut, E.Kale, N.Yost, K.Duffy, C.Hwee, M.Miao, Z.Ashworth, A.Mackall, C.Marson, A.Carnevale, J.Vardhana, S.Satpathy, A.2022-04-21doi:10.1101/2022.04.20.488974Cold Spring Harbor Laboratory Press2022-04-21
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A flexible modeling and inference framework for estimating variant effect sizes from GWAS summary statistics
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https://biorxiv.org/cgi/content/short/2022.04.18.488696v1?rss=1"
Spence, J. P.Sinnott-Armstrong, N.Assimes, T.Pritchard, J. K.2022-04-19doi:10.1101/2022.04.18.488696Cold Spring Harbor Laboratory Press2022-04-19
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Integrative single-cell analysis of cardiogenesis identifies developmental trajectories and non-coding mutations in congenital heart disease
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https://biorxiv.org/cgi/content/short/2022.06.29.498132v1?rss=1"
Ameen, M.Sundaram, L.Banerjee, A.Shen, M.Kundu, S.Nair, S.Shcherbina, A.Gu, M.Wilson, K. D.Varadarajan, A.Vadgama, N.Balsubramani, A.Wu, J. C.Engreitz, J.Farh, K.Karakikes, I.Wang, K. C.Quertermous, T.Greenleaf, W.Kundaje, A.2022-06-29doi:10.1101/2022.06.29.498132Cold Spring Harbor Laboratory Press2022-06-29
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Polygenic enrichment distinguishes disease associations of individual cells in single-cell RNA-seq data
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https://biorxiv.org/cgi/content/short/2021.09.24.461597v1?rss=1"
Zhang, M. J.Hou, K.Dey, K. K.Jagadeesh, K. A.Weinand, K.Sakaue, S.Taychameekiatchai, A.Rao, P.Pisco, A. O.Zou, J.Wang, B.Gandal, M.Raychaudhuri, S.Pasaniuc, B.Price, A. L.2021-09-28doi:10.1101/2021.09.24.461597Cold Spring Harbor Laboratory Press2021-09-28
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Unique contribution of enhancer-driven and master-regulator genes to autoimmune disease revealed using functionally informed SNP-to-gene linking strategies
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https://biorxiv.org/cgi/content/short/2020.09.02.279059v1?rss=1"
2x stronger conditional signal (maximum standardized SNP annotation effect size ({tau}*) = 2.0 (s.e. 0.3) vs. 0.91 (s.e. 0.21)), and >2x stronger gene-level enrichment for approved autoimmune disease drug targets (5.3x vs. 2.1x), as compared to the recently proposed Enhancer Domain Score (EDS). In each case, using functionally informed S2G strategies to link genes to SNPs that may regulate them produced much stronger disease signals (4.1x-13x larger{tau} * values) than conventional window-based S2G strategies. We conclude that our characterizations of enhancer-related and candidate master-regulator genes identify gene sets that are important for autoimmune disease, and that combining those gene sets with functionally informed S2G strategies enables us to identify SNP annotations in which disease heritability is concentrated.
]]>Dey, K. K.Gazal, S. K.van de Geijn, B.Kim, S. S.Nasser, J.Engreitz, J. M.Price, A.2020-09-03doi:10.1101/2020.09.02.279059Cold Spring Harbor Laboratory Press2020-09-03
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Analysis of alternative polyadenylation from long-read or short-read RNA-seq with LAPA
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https://biorxiv.org/cgi/content/short/2022.11.08.515683v1?rss=1"
Celik, M. H.Mortazavi, A.2022-11-08doi:10.1101/2022.11.08.515683Cold Spring Harbor Laboratory Press2022-11-08
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A systematic genotype-phenotype map for missense variants in the human intellectual disability-associated gene GDI1
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https://biorxiv.org/cgi/content/short/2021.10.06.463360v1?rss=1"
Silverstein, R. A.Sun, S. A.Verby, M.Weile, J.Wu, Y.Roth, F. P.2021-10-06doi:10.1101/2021.10.06.463360Cold Spring Harbor Laboratory Press2021-10-06
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MaveDB v2: a curated community database with over three million variant effects from multiplexed functional assays
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https://biorxiv.org/cgi/content/short/2021.11.29.470445v1?rss=1"
Rubin, A. F.Min, J. K.Rollins, N. J.Da, E. Y.Esposito, D.Harrington, M.Stone, J.Bianchi, A. H.Fu, Y.Gallaher, M.Li, I.Moscatelli, O.Ong, J. Y.Rollins, J. E.Wakefield, M. J.Ye, S.Tam, A.McEwen, A. E.Starita, L. M.Bryant, V. L.Marks, D. S.Fowler, D. M.2021-11-30doi:10.1101/2021.11.29.470445Cold Spring Harbor Laboratory Press2021-11-30
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Chemico-genetic Analysis of Native Autism Proteomes Reveals Shared Biology Predictive of Functional Modifiers
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https://biorxiv.org/cgi/content/short/2022.10.06.511211v1?rss=1"
Gao, Y.Trn, M.Shonai, D.Zhao, J.Soderblom, E. J.Garcia-moreno, S. A.Gersbach, C. A.Wetsel, W. C.Dawson, G.Velmeshev, D.Jiang, Y.-h.Sloofman, L.Buxbaum, J.Soderling, S. H.2022-10-07doi:10.1101/2022.10.06.511211Cold Spring Harbor Laboratory Press2022-10-07
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Assessing computational variant effect predictors with a large prospective cohort
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https://biorxiv.org/cgi/content/short/2021.09.20.459182v1?rss=1"
Kuang, D.Li, R.Wu, Y.Weile, J.Hegele, R. A.Roth, F. P.2021-09-20doi:10.1101/2021.09.20.459182Cold Spring Harbor Laboratory Press2021-09-20
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Epo-IGF1R crosstalk expands stress-specific progenitors in regenerative erythropoiesis and myeloproliferative neoplasm
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https://biorxiv.org/cgi/content/short/2022.06.27.497649v1?rss=1"
Huang, L.Hsieh, H.-h.Yao, H.Ma, Y.Zhang, Y.Xiao, X.Stephens, H.Chung, S. S.Xu, L.Xu, J.Rampal, R. K.2022-06-29doi:10.1101/2022.06.27.497649Cold Spring Harbor Laboratory Press2022-06-29
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Massively parallel dissection of human accelerated regions in human and chimpanzee neural progenitors
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https://biorxiv.org/cgi/content/short/256313v1?rss=1"
Ryu, H.Inoue, F.Whalen, S.Williams, A.Kircher, M.Martin, B.Alvarado, B.Samee, M. A. H.Keough, K.Thomas, S.Kriegstein, A.Shendure, J.Pollen, A.Ahituv, N.Pollard, K.2018-01-29doi:10.1101/256313Cold Spring Harbor Laboratory Press2018-01-29
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Integrative dissection of gene regulatory elements at base resolution
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https://biorxiv.org/cgi/content/short/2022.10.05.511030v1?rss=1"
Chen, Z.Javed, N. M.Moore, M.Wu, J.Vinyard, M. E.Pinello, L.Najm, F.Bernstein, B. E.2022-10-06doi:10.1101/2022.10.05.511030Cold Spring Harbor Laboratory Press2022-10-06
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CHD-associated enhancers shape human cardiomyocyte lineage commitment
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https://biorxiv.org/cgi/content/short/2022.04.07.487515v1?rss=1"
Armendariz, D. A.Goetsch, S. C.Wang, Y.Xie, S.Munshi, N. V.Hon, G. C.2022-04-10doi:10.1101/2022.04.07.487515Cold Spring Harbor Laboratory Press2022-04-10
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Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption
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https://biorxiv.org/cgi/content/short/2022.07.26.501609v1?rss=1"
Cooley, A.Madhukaran, S.Stroebele, E.Caraballo, M. C.Wang, L.Hon, G.Mahendroo, M.2022-07-28doi:10.1101/2022.07.26.501609Cold Spring Harbor Laboratory Press2022-07-28
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CROP-Seq: a single-cell CRISPRi platform for characterizing candidate genes relevant to metabolic disorders in human adipocytes
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https://biorxiv.org/cgi/content/short/2022.06.27.497796v1?rss=1"
View larger version (33K):
org.highwire.dtl.DTLVardef@1ee34b6org.highwire.dtl.DTLVardef@1c6ba8aorg.highwire.dtl.DTLVardef@fa89org.highwire.dtl.DTLVardef@403966_HPS_FORMAT_FIGEXP M_FIG C_FIG
]]>Bielczyk-Maczynska, E.Sharma, D.Blencowe, M.Saliba-Gustafsson, P.Gloudemans, M. J.Yang, X.Carcamo-Orive, I.Wabitsch, M.Svensson, K. J.Park, C. Y.Quertermous, T.Knowles, J. W.Li, J.2022-06-27doi:10.1101/2022.06.27.497796Cold Spring Harbor Laboratory Press2022-06-27
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Mapping the convergence of genes for coronary artery disease onto endothelial cell programs
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https://biorxiv.org/cgi/content/short/2022.11.01.514606v1?rss=1"
Schnitzler, G. R.Kang, H.Lee-Kim, V. S.Ma, R. X.Zeng, T.Angom, R. S.Fang, S.Vellarikkal, S. K.Zhou, R.Guo, K.Sias-Garcia, O.Bloemendal, A.Munson, G.Guckelberger, P.Nguyen, T. H.Bergman, D. T.Cheng, N.Cleary, B.Aragam, K.Mukhopadhyay, D.Lander, E. S.Finucane, H. K.Gupta, R. M.Engreitz, J. M.2022-11-04doi:10.1101/2022.11.01.514606Cold Spring Harbor Laboratory Press2022-11-04
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HiCLift: A fast and efficient tool for converting chromatin interaction data between genome assemblies
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https://biorxiv.org/cgi/content/short/2023.01.17.524475v1?rss=1"
Wang, X.Yue, F.2023-01-20doi:10.1101/2023.01.17.524475Cold Spring Harbor Laboratory Press2023-01-20
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Comparing Genomic and Epigenomic Features across Species Using the WashU Comparative Epigenome Browser
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https://biorxiv.org/cgi/content/short/2022.11.29.518374v1?rss=1"
Zhuo, X.Hsu, S.Purushotham, D.Chen, S.Li, D.Wang, T.2022-12-02doi:10.1101/2022.11.29.518374Cold Spring Harbor Laboratory Press2022-12-02
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A machine-readable specification for genomics assays
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https://biorxiv.org/cgi/content/short/2023.03.17.533215v1?rss=1"
Booeshaghi, A. S.Chen, X.Pachter, L.2023-03-21doi:10.1101/2023.03.17.533215Cold Spring Harbor Laboratory Press2023-03-21
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Dynamic network-guided CRISPRi screen reveals CTCF loop-constrained nonlinear enhancer-gene regulatory activity in cell state transitions
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https://biorxiv.org/cgi/content/short/2023.03.07.531569v1?rss=1"
Luo, R.Yan, J.Oh, J. W.Xi, W.Shigaki, D.Wong, W.Cho, H.Murphy, D.Cutler, R.Rosen, B. P.Pulecio, J.Yang, D.Glenn, R.Chen, T.Li, Q. V.Vierbuchen, T.Sidoli, S.Apostolou, E.Huangfu, D.Beer, M. A.2023-03-09doi:10.1101/2023.03.07.531569Cold Spring Harbor Laboratory Press2023-03-09
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Orthogonal CRISPR screens to identify transcriptional and epigenetic regulators of human CD8 T cell function
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https://biorxiv.org/cgi/content/short/2023.05.01.538906v1?rss=1"
McCutcheon, S.Swartz, A.Brown, M.Barrera, A.McRoberts Amador, C.Siklenka, K.Humayun, L.Isaacs, J.Reddy, T. E.Nair, S.Antonia, S.Gersbach, C. A.2023-05-01doi:10.1101/2023.05.01.538906Cold Spring Harbor Laboratory Press2023-05-01
<![CDATA[
Transcription factor stoichiometry, motif affinity and syntax regulate single-cell chromatin dynamics during fibroblast reprogramming to pluripotency
]]>
https://biorxiv.org/cgi/content/short/2023.10.04.560808v1?rss=1"
Nair, S.Ameen, M.Sundaram, L.Pampari, A.Schreiber, J.Balsubramani, A.Wang, Y. X.Burns, D.Blau, H. M.Karakikes, I.Wang, K. C.Kundaje, A.2023-10-04doi:10.1101/2023.10.04.560808Cold Spring Harbor Laboratory Press2023-10-04
<![CDATA[
Reconstructing Spatial Transcriptomics at the Single-cell Resolution with BayesDeep
]]>
https://biorxiv.org/cgi/content/short/2023.12.07.570715v1?rss=1"
Jiang, X.Dong, L.Wang, S.Wen, Z.Chen, M.Xu, L.Xiao, G.Li, Q.2023-12-08doi:10.1101/2023.12.07.570715Cold Spring Harbor Laboratory Press2023-12-08
<![CDATA[
MPRAbase: A Massively Parallel Reporter Assay Database
]]>
https://biorxiv.org/cgi/content/short/2023.11.19.567742v1?rss=1"
Zhao, J.Baltoumas, F. A.Konnaris, M. A.Mouratidis, I.Liu, Z.Sims, J.Agarwal, V.Pavlopoulos, G. A.Georgakopoulos-Soares, I.Ahituv, N.2023-11-22doi:10.1101/2023.11.19.567742Cold Spring Harbor Laboratory Press2023-11-22
<![CDATA[
Chromatin context-dependent regulation and epigenetic manipulation of prime editing
]]>
https://biorxiv.org/cgi/content/short/2023.04.12.536587v1?rss=1"
Li, X.Chen, W.Martin, B. K.Calderon, D.Lee, C.Choi, J.Chardon, F. M.McDiarmid, T.Kim, H.Lalanne, J.-B.Nathans, J. F.Shendure, J.2023-04-12doi:10.1101/2023.04.12.536587Cold Spring Harbor Laboratory Press2023-04-12
<![CDATA[
Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements
]]>
https://biorxiv.org/cgi/content/short/2023.03.28.534017v1?rss=1"
Chardon, F. M.McDiarmid, T. A.Page, N. F.Martin, B. K.Domcke, S.Regalado, S. G.Lalanne, J.-B.Calderon, D.Starita, L. M.Sanders, S. J.Ahituv, N.Shendure, J.2023-03-28doi:10.1101/2023.03.28.534017Cold Spring Harbor Laboratory Press2023-03-28
<![CDATA[
Massively parallel characterization of transcriptional regulatory elements in three diverse human cell types
]]>
https://biorxiv.org/cgi/content/short/2023.03.05.531189v1?rss=1"
Agarwal, V.Inoue, F.Schubach, M.Martin, B.Dash, P.Zhang, Z.Sohota, A.Noble, W.Yardimci, G.Kircher, M.Shendure, J.Ahituv, N.2023-03-06doi:10.1101/2023.03.05.531189Cold Spring Harbor Laboratory Press2023-03-06
<![CDATA[
Massively parallel characterization of psychiatric disorder-associated and cell-type-specific regulatory elements in the developing human cortex
]]>
https://biorxiv.org/cgi/content/short/2023.02.15.528663v1?rss=1"
Deng, C.Whalen, S.Steyert, M.Ziffra, R.Przytycki, P. F.Inoue, F.Pereira, D. A.Capauto, D.Norton, S.Vaccarino, F. M.Pollen, A. A.Nowakowski, T. J.Ahituv, N. A.Pollard, K. S.2023-02-15doi:10.1101/2023.02.15.528663Cold Spring Harbor Laboratory Press2023-02-15
<![CDATA[
Multiplex profiling of developmental enhancers with quantitative, single-cell expression reporters
]]>
https://biorxiv.org/cgi/content/short/2022.12.10.519236v1?rss=1"
10,000-fold range of activity with a precision approaching the limit set by Poisson counting noise. Together with RNA barcode circularization, these single-cell quantitative expression reporters (scQers) provide high-contrast readouts analogous to classic in situ assays, but entirely from sequencing. Screening >200 enhancers in a multicellular in vitro model of early mammalian development, we identified numerous autonomous and cell-type-specific elements, including constituents of the Sox2 control region exclusively active in pluripotent cells, endoderm-specific enhancers, including near Foxa2 and Gata4, and a compact pleiotropic enhancer at the Lamc1 locus. scQers can be mobilized in developmental systems to quantitatively characterize native, perturbed, and synthetic enhancers at scale, with high sensitivity and at single-cell resolution.
]]>Lalanne, J.-B.Regalado, S. G.Domcke, S.Calderon, D.Martin, B.Li, T.Suiter, C. C.Lee, C.Trapnell, C.Shendure, J. A.2022-12-10doi:10.1101/2022.12.10.519236Cold Spring Harbor Laboratory Press2022-12-10
<![CDATA[
Pacybara: Accurate long-read sequencing for barcoded mutagenized allelic libraries
]]>
https://biorxiv.org/cgi/content/short/2023.02.22.529427v1?rss=1"
Weile, J.Cote, A. G.Kishore, N.Tabet, D.van Loggerenberg, W.Rayhan, A.Roth, F. P.2023-02-23doi:10.1101/2023.02.22.529427Cold Spring Harbor Laboratory Press2023-02-23
<![CDATA[
Assigning credit where it's due: An information content score to capture the clinical value of Multiplexed Assays of Variant Effect
]]>
https://biorxiv.org/cgi/content/short/2023.10.20.562794v1?rss=1"
Ranola, J. M.Horton, C.Pesaran, T.Fayer, S.Starita, L. M.Shirts, B. H.2023-10-20doi:10.1101/2023.10.20.562794Cold Spring Harbor Laboratory Press2023-10-20
<![CDATA[
Mapping MAVE data for use in human genomics applications
]]>
https://biorxiv.org/cgi/content/short/2023.06.20.545702v1?rss=1"
Arbesfeld, J. A.Da, E. Y.Kuzma, K.Paul, A.Farris, T.Riehle, K.Agostinho, N. D. S.Safer, J. F.Milosavljevic, A.Foreman, J.Firth, H. V.Hunt, S. E.Iqbal, S.Cline, M.Rubin, A. F.Wagner, A. H.2023-06-23doi:10.1101/2023.06.20.545702Cold Spring Harbor Laboratory Press2023-06-23
<![CDATA[
Genomics 2 Proteins portal: A resource and discovery tool for linking genetic screening outputs to protein sequences and structures
]]>
https://biorxiv.org/cgi/content/short/2024.01.02.573913v1?rss=1"
Kwon, S.Safer, J.Nguyen, D. T.Hoksza, D.May, P.Arbesfeld, J.Rubin, A. F.Campbell, A. J.Burgin, A.Iqbal, S.2024-01-02doi:10.1101/2024.01.02.573913Cold Spring Harbor Laboratory Press2024-01-02
<![CDATA[
Integrating deep mutational scanning and low-throughput mutagenesis data to predict the impact of amino acid variants
]]>
https://biorxiv.org/cgi/content/short/2022.12.14.520494v1?rss=1"
Fu, Y.Bedo, J.Papenfuss, A. T.Rubin, A. F.2022-12-16doi:10.1101/2022.12.14.520494Cold Spring Harbor Laboratory Press2022-12-16
<![CDATA[
An encyclopedia of enhancer-gene regulatory interactions in the human genome
]]>
https://biorxiv.org/cgi/content/short/2023.11.09.563812v1?rss=1"
13 million enhancer-gene regulatory interactions across 352 cell types and tissues, by integrating predictive models, measurements of chromatin state and 3D contacts, and large-scale genetic perturbations generated by the ENCODE Consortium7. We first create a systematic benchmarking pipeline to compare predictive models, assembling a dataset of 10,411 element-gene pairs measured in CRISPR perturbation experiments, >30,000 fine-mapped eQTLs, and 569 fine-mapped GWAS variants linked to a likely causal gene. Using this framework, we develop a new predictive model, ENCODE-rE2G, that achieves state-of-the-art performance across multiple prediction tasks, demonstrating a strategy involving iterative perturbations and supervised machine learning to build increasingly accurate predictive models of enhancer regulation. Using the ENCODE-rE2G model, we build an encyclopedia of enhancer-gene regulatory interactions in the human genome, which reveals global properties of enhancer networks, identifies differences in the functions of genes that have more or less complex regulatory landscapes, and improves analyses to link noncoding variants to target genes and cell types for common, complex diseases. By interpreting the model, we find evidence that, beyond enhancer activity and 3D enhancer-promoter contacts, additional features guide enhancer-promoter communication including promoter class and enhancer-enhancer synergy. Altogether, these genome-wide maps of enhancer-gene regulatory interactions, benchmarking software, predictive models, and insights about enhancer function provide a valuable resource for future studies of gene regulation and human genetics.
]]>Gschwind, A. R.Mualim, K. S.Karbalayghareh, A.Sheth, M. U.Dey, K. K.Jagoda, E.Nurtdinov, R. N.Xi, W.Tan, A. S.Jones, H.Ma, X. R.Yao, D.Nasser, J.Avsec, Z.James, B. T.Shamim, M. S.Durand, N. C.Rao, S. S. P.Mahajan, R.Doughty, B. R.Andreeva, K.Ulirsch, J. C.Fan, K.Perez, E. M.Nguyen, T. C.Kelley, D. R.Finucane, H. K.Moore, J. E.Weng, Z.Kellis, M.Bassik, M. C.Price, A. L.Beer, M. A.Guigo, R.Stamatoyannopoulos, J. A.Aiden, E. L.Greenleaf, W. J.Leslie, C. S.Steinmetz, L. M.Kundaje, A.Engreitz, J. M.2023-11-13doi:10.1101/2023.11.09.563812Cold Spring Harbor Laboratory Press2023-11-13
<![CDATA[
Single-cell transcriptome dataset of human and mouse in vitro adipogenesis models
]]>
https://biorxiv.org/cgi/content/short/2023.03.27.534456v1?rss=1"
Li, J.Jin, C.Gustafsson, S.Rao, A.Wabitsch, M.Park, C. Y.Quertermous, T.Bielczyk-Maczynska, E.Knowles, J. W.2023-03-29doi:10.1101/2023.03.27.534456Cold Spring Harbor Laboratory Press2023-03-29
<![CDATA[
Rewriting regulatory DNA to dissect and reprogram gene expression
]]>
https://biorxiv.org/cgi/content/short/2023.12.20.572268v1?rss=1"
Martyn, G. E.Montgomery, M. T.Jones, H.Guo, K.Doughty, B. R.Linder, J.Chen, Z.Cochran, K.Lawrence, K. A.Munson, G.Pampari, A.Fulco, C. P.Kelley, D. R.Lander, E. S.Kundaje, A.Engreitz, J. M.2023-12-21doi:10.1101/2023.12.20.572268Cold Spring Harbor Laboratory Press2023-12-21
<![CDATA[
SLC12A9 is a lysosome-detoxifying ammonium - chloride co-transporter
]]>
https://biorxiv.org/cgi/content/short/2023.05.22.541801v1?rss=1"
Levin-Konigsberg, R.Mitra, K.Nigam, A.Spees, K.Hivare, P.Liu, K.Kundaje, A.Krishnan, Y.Bassik, M.2023-05-22doi:10.1101/2023.05.22.541801Cold Spring Harbor Laboratory Press2023-05-22
<![CDATA[
Molecular mechanisms of coronary artery disease risk at the PDGFD locus
]]>
https://biorxiv.org/cgi/content/short/2023.01.26.525789v1?rss=1"
Kim, H.-J.Cheng, P.Travisano, S.Weldy, C. S.Monteiro, J.Kundu, R.Nguyen, T.Sharma, D.Shi, H.Liu, B.Lin, Y.Haldar, S.Jackson, S.Quertermous, T.2023-01-27doi:10.1101/2023.01.26.525789Cold Spring Harbor Laboratory Press2023-01-27
<![CDATA[
The epigenomic landscape of single vascular cells reflects developmental origin and identifies disease risk loci
]]>
https://biorxiv.org/cgi/content/short/2022.05.18.492517v1?rss=1"
Weldy, C. S.Cheng, P. P.Pedroza, A. J.Dalal, A. R.Sharma, D.Kim, H.-J.Shi, H.Nguyen, T.Kundu, R. K.Fischbein, M. P.Quertermous, T.2022-05-18doi:10.1101/2022.05.18.492517Cold Spring Harbor Laboratory Press2022-05-18
<![CDATA[
Pervasive mislocalization of pathogenic coding variants underlying human disorders
]]>
https://biorxiv.org/cgi/content/short/2023.09.05.556368v1?rss=1"
Lacoste, J.Haghighi, M.Haider, S.Lin, Z.-Y.Segal, D.Reno, C.Qian, W. W.Xiong, X.Shafqat-Abbasi, H.Ryder, P.Senft, R.Cimini, B.Roth, F.Calderwood, M.Hill, D.Vidal, M.Yi, S.Sahni, N.Peng, J.Gingras, A.-C.Singh, S.Carpenter, A.Taipale, M.2023-09-05doi:10.1101/2023.09.05.556368Cold Spring Harbor Laboratory Press2023-09-05
<![CDATA[
Characterizing glucokinase variant mechanisms using a multiplexed abundance assay
]]>
https://biorxiv.org/cgi/content/short/2023.05.24.542036v1?rss=1"
Gersing, S.Schulze, T. K.Cagiada, M.Stein, A.Roth, F. P.Lindorff-Larsen, K.Hartmann-Petersen, R.2023-05-24doi:10.1101/2023.05.24.542036Cold Spring Harbor Laboratory Press2023-05-24
<![CDATA[
Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation
]]>
https://biorxiv.org/cgi/content/short/2023.02.06.527353v1?rss=1"
84% of all possible amino-acid substitutions. The resulting variant effect maps generally agreed with biochemical expectation. However, the maps showed variants at the dimerization interface to be unexpectedly well tolerated, and suggested residue roles in active site dynamics that were supported by molecular dynamics simulations. Most importantly, these HMBS variant effect maps can help discriminate pathogenic from benign variants, proactively providing evidence even for yet-to-be-observed clinical missense variants.
]]>van Loggerenberg, W.Sowlati-Hashjin, S.Weile, J.Hamilton, R.Chawla, A.Gebbia, M.Kishore, N.Fresard, L.Mustajoki, S.Pischik, E.Di Pierro, E.Barbaro, M.Floderus, Y.Schmitt, C.Gouya, L.Colavin, A.Nussbaum, R.Friesema, E. C. H.Kauppinen, R.To-Figueras, J.Aarsand, A. K.Desnick, R. J.Garton, M.Roth, F. P.2023-02-06doi:10.1101/2023.02.06.527353Cold Spring Harbor Laboratory Press2023-02-06
<![CDATA[
Integrating Image and Molecular Profiles for Spatial Transcriptomics Analysis
]]>
https://biorxiv.org/cgi/content/short/2023.06.18.545488v1?rss=1"
Jiang, X.Wang, S.Guo, L.Wen, Z.Jia, L.Xu, L.Xiao, G.Li, Q.2023-06-20doi:10.1101/2023.06.18.545488Cold Spring Harbor Laboratory Press2023-06-20
<![CDATA[
Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes
]]>
https://biorxiv.org/cgi/content/short/2023.11.20.567880v1?rss=1"
500,000 single-cell transcriptomes in two breast cancer cell lines shows that perturbation of variant-associated enhancers disrupts breast cancer gene programs. We observe variant-associated enhancers that directly or indirectly regulate the expression of cancer genes. We also find one-to-multiple and multiple-to-one network motifs where enhancers indirectly regulate cancer genes. Notably, multiple variant-associated enhancers indirectly regulate TP53. Comparative studies illustrate sub-type specific functions between enhancers in ER+ and ER- cells. Finally, we developed the pySpade package to facilitate analysis of single-cell enhancer screens. Overall, we demonstrate that enhancers form regulatory networks that link cancer genes in the genome, providing a more comprehensive understanding of the contribution of enhancers to breast cancer development.
]]>Wang, Y.Armendariz, D. A.Wang, L.Zhao, H.Xie, S.Hon, G. C.2023-11-20doi:10.1101/2023.11.20.567880Cold Spring Harbor Laboratory Press2023-11-20
<![CDATA[
Dissecting embryonic and extra-embryonic lineage crosstalk with stem cell co-culture
]]>
https://biorxiv.org/cgi/content/short/2023.03.07.531525v1?rss=1"
Wu, J.Wei, Y.Zhang, E.Yu, L.Guo, L.Sakurai, M.Takii, S.Schmitz, D.Ding, Y.Zheng, C.Sun, H.Xu, L.Okamura, D.Ji, W.Tan, T.Zhan, L.Ci, B.Liu, J.2023-03-07doi:10.1101/2023.03.07.531525Cold Spring Harbor Laboratory Press2023-03-07
<![CDATA[
Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness
]]>
https://biorxiv.org/cgi/content/short/2024.01.10.574997v1?rss=1"
Cosgrove, B. D.Bounds, L. R.Taylor, C. K.Su, A. L.Rizzo, A. J.Barrera, A.Crawford, G. E.Hoffman, B. D.Gersbach, C. A.2024-01-10doi:10.1101/2024.01.10.574997Cold Spring Harbor Laboratory Press2024-01-10
<![CDATA[
Single-cell multi-scale footprinting reveals the modular organization of DNA regulatory elements
]]>
https://biorxiv.org/cgi/content/short/2023.03.28.533945v1?rss=1"
Hu, Y.Ma, S.Kartha, V. K.Duarte, F. M.Horlbeck, M.Zhang, R.Shrestha, R.Labade, A.Kletzien, H.Meliki, A.Castillo, A.Durand, N.Mattei, E.Anderson, L. J.Tay, T.Earl, A. S.Shoresh, N.Epstein, C. B.Wagers, A.Buenrostro, J. D.2023-03-29doi:10.1101/2023.03.28.533945Cold Spring Harbor Laboratory Press2023-03-29
<![CDATA[
Convergent Epigenetic Evolution Drives Relapse in Acute Myeloid Leukemia
]]>
https://biorxiv.org/cgi/content/short/2023.10.10.561642v1?rss=1"
Nuno, K.Azizi, A.Koehnke, T.Lareau, C.Ediriwickrema, A.Corces, M. R.Satpathy, A. T.Majeti, R.2023-10-10doi:10.1101/2023.10.10.561642Cold Spring Harbor Laboratory Press2023-10-10
<![CDATA[
Single-cell multi-omics reveals dynamics of purifying selection of pathogenic mitochondrial DNA across human immune cells
]]>
https://biorxiv.org/cgi/content/short/2022.11.20.517242v1?rss=1"
Lareau, C. A.Dubois, S. M.Buquicchio, F. A.Hsieh, Y.-H.Garg, K.Kautz, P.Nitsch, L.Praktiknjo, S. D.Maschmeyer, P.Verboon, J. M.Gutierrez, J. C.Yin, Y.Fiskin, E.Luo, W.Mimitou, E.Muus, C.Malhotra, R.Parikh, S.Fleming, M. D.Oevermann, L.Schulte, J.Eckert, C.Kundaje, A.Smibert, P.Satpathy, A. T.Regev, A.Sankaran, V. G.Agarwal, S.Ludwig, L. S.2022-11-20doi:10.1101/2022.11.20.517242Cold Spring Harbor Laboratory Press2022-11-20
<![CDATA[
Codon affinity in mitochondrial DNA shapes evolutionary and somatic fitness
]]>
https://biorxiv.org/cgi/content/short/2023.04.23.537997v1?rss=1"
G) in the mitochondrial DNA (mtDNA) encoded cytochrome c-oxidase subunit 1 gene (MT-CO1, p.Gly391=), which was present at homoplasmy in 47% of immune cells from a healthy donor. Using single-cell multi-omics, we discover highly specific selection against the m.7076G mutant allele in the CD8+ effector memory T cell compartment in vivo, reminiscent of selection observed for pathogenic mtDNA alleles1, 2 and indicative of lineage-specific metabolic requirements. While the wildtype m.7076A allele is translated via Watson-Crick-Franklin base-pairing, the anticodon diversity of the mitochondrial transfer RNA pool is limited, requiring wobble-dependent translation of the m.7076G mutant allele. Notably, mitochondrial ribosome profiling revealed altered codon-anticodon affinity at the wobble position as evidenced by stalled translation of the synonymous m.7076G mutant allele encoding for glycine. Generalizing this observation, we provide a new ontogeny of the 8,482 synonymous variants in the human mitochondrial genome that enables interpretation of functional mtDNA variation. Specifically, via inter- and intra-species evolutionary analyses, population-level complex trait associations, and the occurrence of germline and somatic mtDNA mutations from large-scale sequencing studies, we demonstrate that synonymous variation impacting codon:anticodon affinity is actively evolving across the entire mitochondrial genome and has broad functional and phenotypic effects. In summary, our results introduce a new ontogeny for mitochondrial genetic variation and support a model where organismal principles can be discerned from somatic evolution via single-cell genomics.
]]>Lareau, C. A.Yin, Y.Gutierrez, J. C.Dhindsa, R. S.Gribling-Burrer, A.-S.Hsieh, Y.-H.Nitsch, L.Buquicchio, F. A.Abay, T.Zielinski, S.Stickels, R. R.Ulirsch, J. C.Yan, P.Wang, F.Miao, Z.Sandor, K.Daniel, B.Liu, V.Wang, Q.Hu, F.Smith, K. R.Deevi, S. V. V.Maschmeyer, P.Petrovski, S.Smyth, R. P.Greenleaf, W. J.Kundaje, A.Munschauer, M.Ludwig, L. S.Satpathy, A. T.2023-04-23doi:10.1101/2023.04.23.537997Cold Spring Harbor Laboratory Press2023-04-23
<![CDATA[
Identifying genetic variants that influence the abundance of cell states in single-cell data
]]>
https://biorxiv.org/cgi/content/short/2023.11.13.566919v1?rss=1"
Rumker, L.Sakaue, S.Reshef, Y.Kang, J. B.Yazar, S.Alquicira-Hernandez, J.Valencia, C.Lagattuta, K. A.Mah-Som, A.Nathan, A.Powell, J. E.Loh, P.-R.Raychaudhuri, S.2023-11-15doi:10.1101/2023.11.13.566919Cold Spring Harbor Laboratory Press2023-11-15
<![CDATA[
Uncovering context-specific genetic-regulation of gene expression from single-cell RNA-sequencing using latent-factor models
]]>
https://biorxiv.org/cgi/content/short/2022.12.22.521678v1?rss=1"
Strober, B. J.Tayeb, K.Popp, J.Qi, G.Gordon, M. G.Perez, R.Ye, C. J.Battle, A.2022-12-23doi:10.1101/2022.12.22.521678Cold Spring Harbor Laboratory Press2022-12-23
<![CDATA[
Reimagining Gene-Environment Interaction Analysis for Human Complex Traits
]]>
https://biorxiv.org/cgi/content/short/2022.12.11.519973v1?rss=1"
Miao, J.Song, G.Wu, Y.Hu, J.Wu, Y.Basu, S.Andrews, J. S.Schaumberg, K.Fletcher, J. M.Schmitz, L. L.Lu, Q.2022-12-14doi:10.1101/2022.12.11.519973Cold Spring Harbor Laboratory Press2022-12-14
<![CDATA[
Leveraging a machine learning derived surrogate phenotype to improve power for genome-wide association studies of partially missing phenotypes in population biobanks
]]>
https://biorxiv.org/cgi/content/short/2022.12.12.520180v1?rss=1"
McCaw, Z. R.Gao, J. R.Lin, X.Gronsbell, J.2022-12-14doi:10.1101/2022.12.12.520180Cold Spring Harbor Laboratory Press2022-12-14
<![CDATA[
Ensembled best subset selection using summary statistics for polygenic risk prediction
]]>
https://biorxiv.org/cgi/content/short/2023.09.25.559307v1?rss=1"
Chen, T.Zhang, H.Mazumder, R.Lin, X.2023-09-26doi:10.1101/2023.09.25.559307Cold Spring Harbor Laboratory Press2023-09-26
<![CDATA[
A statistical framework for powerful multi-trait rare variant analysis in large-scale whole-genome sequencing studies
]]>
https://biorxiv.org/cgi/content/short/2023.10.30.564764v1?rss=1"
Li, X.Chen, H.Selvaraj, M. S.Van Buren, E.Zhou, H.Wang, Y.Sun, R.McCaw, Z. R.Yu, Z.Arnett, D. K.Bis, J. C.Blangero, J.Boerwinkle, E.Bowden, D. W.Brody, J. A.Cade, B. E.Carson, A. P.Carlson, J. C.Chami, N.Chen, Y.-D. I.Curran, J. E.de Vries, P. S.Fornage, M.Franceschini, N.Freedman, B. I.Gu, C.Heard-Costa, N. L.He, J.Hou, L.Hung, Y.-J.Irvin, M. R.Kaplan, R. C.Kardia, S. L. R.Kelly, T.Konigsberg, I.Kooperberg, C.Kral, B. G.Li, C.Loos, R. J. F.Mahaney, M. C.Martin, L. W.Mathias, R. A.Minster, R. L.Mitchell, B. D2023-11-02doi:10.1101/2023.10.30.564764Cold Spring Harbor Laboratory Press2023-11-02
<![CDATA[
Whole Genome Sequencing Based Analysis of Inflammation Biomarkers in the Trans-Omics for Precision Medicine (TOPMed) Consortium
]]>
https://biorxiv.org/cgi/content/short/2023.09.10.555215v1?rss=1"
Jiang, M.-Z.Gaynor, S. M.Li, X.Van Buren, E.Stilp, A.Buth, E.Wang, F. F.Manansala, R.Gogarten, S. M.Li, Z.Polfus, L. M.Salimi, S.Bis, J. C.Pankratz, N.Yanek, L. R.Durda, P.Tracy, R. P.Rich, S. S.Rotter, J. I.Mitchell, B. D.Lewis, J. P.Psaty, B. M.Pratte, K. A.Silverman, E. K.Kaplan, R. C.Avery, C.North, K.Mathias, R. A.Faraday, N.Lin, H.Wang, B.Carson, A. P.Norwood, A. F.Gibbs, R. A.Kooperberg, C.Lundin, J.Peters, U.Dupuis, J.Hou, L.Fornage, M.Benjamin, E. J.Reiner, A. P.Bowler, R. P.Lin, X.Auer, P. L.Raf2023-09-12doi:10.1101/2023.09.10.555215Cold Spring Harbor Laboratory Press2023-09-12
<![CDATA[
Novel Methods for Multi-ancestry Polygenic Prediction and their Evaluations in 3.7 Million Individuals of Diverse Ancestry
]]>
https://biorxiv.org/cgi/content/short/2022.03.24.485519v1?rss=1"
Zhang, H.Zhan, J.Jin, J.Ahearn, T. U.Yu, Z.O'Connell, J.Jiang, Y.Chen, T.23andMe Research Team,Garcia-Closas, M.Lin, X.Koelsch, B. L.Chatterjee, N.2022-03-27doi:10.1101/2022.03.24.485519Cold Spring Harbor Laboratory Press2022-03-27
<![CDATA[
Accurate and Efficient Estimation of Local Heritability using Summary Statistics and LD Matrix
]]>
https://biorxiv.org/cgi/content/short/2023.02.08.527759v1?rss=1"
Li, H.Mazumder, R.Lin, X.2023-02-09doi:10.1101/2023.02.08.527759Cold Spring Harbor Laboratory Press2023-02-09
<![CDATA[
De novo distillation of thermodynamic affinity from deep learning regulatory sequence models of in vivo protein-DNA binding
]]>
https://biorxiv.org/cgi/content/short/2023.05.11.540401v1?rss=1"
Alexandari, A. M.Horton, C. A.Shrikumar, A.Shah, N.Li, E.Weilert, M.Pufall, M. A.Zeitlinger, J.Fordyce, P. M.Kundaje, A.2023-05-11doi:10.1101/2023.05.11.540401Cold Spring Harbor Laboratory Press2023-05-11
<![CDATA[
5-hydroxymethylcytosines regulate gene expression as a passive DNA demethylation resisting epigenetic mark in proliferative somatic cells
]]>
https://biorxiv.org/cgi/content/short/2023.09.26.559662v1?rss=1"
Wei, A.Zhang, H.Qiu, Q.Fabyanic, E. B.Hu, P.Wu, H.2023-09-27doi:10.1101/2023.09.26.559662Cold Spring Harbor Laboratory Press2023-09-27
<![CDATA[
A transient dermal niche and dual epidermal programs underlie sweat gland development
]]>
https://biorxiv.org/cgi/content/short/2023.04.15.537037v1?rss=1"
Dingwall, H. L.Tomizawa, R. R.Aharoni, A.Hu, P.Qiu, Q.Kokalari, B.Martinez, S. M.Donahue, J. C.Aldea, D.Mendoza, M.Glass, I. A.Birth Defects Research Laboratory,Wu, H.Kamberov, Y. G.2023-04-17doi:10.1101/2023.04.15.537037Cold Spring Harbor Laboratory Press2023-04-17
<![CDATA[
Decoding Heterogenous Single-cell Perturbation Responses
]]>
https://biorxiv.org/cgi/content/short/2023.10.30.564796v1?rss=1"
Song, B.Liu, D.Dai, W.McMyn, N.Wang, Q.Yang, D.Krejci, A.Vasilyev, A.Untermoser, N.Loregger, A.Song, D.Williams, B.Rosen, B.Cheng, X.Chao, L.Kale, H.Zhang, H.Diao, Y.Bürckstümmer, T.Siliciano, J. M.Li, J. J.Siliciano, R.Huangfu, D.Li, W.2023-11-02doi:10.1101/2023.10.30.564796Cold Spring Harbor Laboratory Press2023-11-02
<![CDATA[
Discovery of Competent Chromatin Regions in Human Embryonic Stem Cells
]]>
https://biorxiv.org/cgi/content/short/2023.06.14.544990v1?rss=1"
Pulecio, J.Tayyebi, Z.Liu, D.Wong, W.Luo, R.Damodaran, J. R.Kaplan, S.Cho, H.Yan, J.Murphy, D. J.Rickert, R.Shukla, A.Zhong, A.Gonzalez, F.Yang, D.Li, W.Zhou, T.Apostolou, E.Leslie, C.Huangfu, D.2023-06-14doi:10.1101/2023.06.14.544990Cold Spring Harbor Laboratory Press2023-06-14
<![CDATA[
Parallel genome-scale CRISPR screens distinguish pluripotency and self-renewal
]]>
https://biorxiv.org/cgi/content/short/2023.05.03.539283v1?rss=1"
Rosen, B. P.Li, Q. V.Cho, H.Liu, D.Yang, D.Graff, S.Yan, J.Luo, R.Verma, N.Damodaran, J. R.Beer, M. A.Sidoli, S.Huangfu, D.2023-05-03doi:10.1101/2023.05.03.539283Cold Spring Harbor Laboratory Press2023-05-03
<![CDATA[
Interface-guided phenotyping of coding variants in the transcription factor RUNX1 with SEUSS
]]>
https://biorxiv.org/cgi/content/short/2023.08.03.551876v1?rss=1"
Ozturk, K.Panwala, R.Sheen, J.Ford, K.Payne, N.Zhang, D.-E.Hutter, S.Haferlach, T.Ideker, T.Mali, P.Carter, H.2023-08-04doi:10.1101/2023.08.03.551876Cold Spring Harbor Laboratory Press2023-08-04
<![CDATA[
Universal chromatin state annotation of the mouse genome
]]>
https://biorxiv.org/cgi/content/short/2022.12.19.521116v1?rss=1"
Vu, H. T.Ernst, J.2022-12-20doi:10.1101/2022.12.19.521116Cold Spring Harbor Laboratory Press2022-12-20
<![CDATA[
Integrative epigenomic and functional characterization assay based annotation of regulatory activity across diverse human cell types
]]>
https://biorxiv.org/cgi/content/short/2023.07.14.549056v1?rss=1"
Dincer, T. U.Ernst, J.2023-07-15doi:10.1101/2023.07.14.549056Cold Spring Harbor Laboratory Press2023-07-15
<![CDATA[
ChromaFold predicts the 3D contact map from single-cell chromatin accessibility
]]>
https://biorxiv.org/cgi/content/short/2023.07.27.550836v1?rss=1"
Gao, V. R.Yang, R.Das, A.Luo, R.Luo, H.McNally, D. R.Karagiannidis, I.Rivas, M. A.Wang, Z.-m.Barisic, D.Karbalayghareh, A.Wong, W.Zhan, Y.Chin, C. R.Noble, W. S.Bilmes, J. A.Apostolou, E.Kharas, M.Beguelin, W.Viny, A. D.Huangfu, D.Rudensky, A.Melnick, A.Leslie, C. S.2023-07-28doi:10.1101/2023.07.27.550836Cold Spring Harbor Laboratory Press2023-07-28
<![CDATA[
Flexible parsing and preprocessing of technical sequences with splitcode
]]>
https://biorxiv.org/cgi/content/short/2023.03.20.533521v1?rss=1"
Sullivan, D. K.Pachter, L.2023-03-23doi:10.1101/2023.03.20.533521Cold Spring Harbor Laboratory Press2023-03-23
<![CDATA[
Universal preprocessing of single-cell genomics data
]]>
https://biorxiv.org/cgi/content/short/2023.09.14.543267v1?rss=1"
Booeshaghi, A. S.Sullivan, D. K.Pachter, L.2023-09-15doi:10.1101/2023.09.14.543267Cold Spring Harbor Laboratory Press2023-09-15
<![CDATA[
kallisto, bustools, and kb-python for quantifying bulk, single-cell, and single-nucleus RNA-seq
]]>
https://biorxiv.org/cgi/content/short/2023.11.21.568164v1?rss=1"
Sullivan, D. K.Min, K. H.Hjörleifsson, K. E.Luebbert, L.Holley, G.Moses, L.Gustafsson, J.Bray, N. L.Pimentel, H.Booeshaghi, A. S.Melsted, P.Pachter, L.2023-11-22doi:10.1101/2023.11.21.568164Cold Spring Harbor Laboratory Press2023-11-22
<![CDATA[
Efficient pre-processing of Single-cell ATAC-seq data
]]>
https://biorxiv.org/cgi/content/short/2021.12.08.471788v1?rss=1"
Gao, F.Pachter, L.2021-12-10doi:10.1101/2021.12.08.471788Cold Spring Harbor Laboratory Press2021-12-10
<![CDATA[
Biophysically Interpretable Inference of Cell Types from Multimodal Sequencing Data
]]>
https://biorxiv.org/cgi/content/short/2023.09.17.558131v1?rss=1"
Chari, T.Gorin, G.Pachter, L.2023-09-17doi:10.1101/2023.09.17.558131Cold Spring Harbor Laboratory Press2023-09-17
<![CDATA[
Voyager: exploratory single-cell genomics data analysis with geospatial statistics
]]>
https://biorxiv.org/cgi/content/short/2023.07.20.549945v1?rss=1"
Moses, L.Einarsson, P. H.Jackson, K. C.Luebbert, L.Booeshaghi, A. S.Antonsson, S. E.Melsted, P.Pachter, L.2023-07-22doi:10.1101/2023.07.20.549945Cold Spring Harbor Laboratory Press2023-07-22
<![CDATA[
Mechanistic modeling with a variational autoencoder for multimodal single-cell RNA sequencing data
]]>
https://biorxiv.org/cgi/content/short/2023.01.13.523995v1?rss=1"
Carilli, M. T.Gorin, G.Choi, Y.Chari, T.Pachter, L.2023-01-14doi:10.1101/2023.01.13.523995Cold Spring Harbor Laboratory Press2023-01-14
<![CDATA[
Monod: mechanistic analysis of single-cell RNA sequencing count data
]]>
https://biorxiv.org/cgi/content/short/2022.06.11.495771v1?rss=1"
Gorin, G.Pachter, L.2022-06-12doi:10.1101/2022.06.11.495771Cold Spring Harbor Laboratory Press2022-06-12
<![CDATA[
Studying stochastic systems biology of the cell with single-cell genomics data
]]>
https://biorxiv.org/cgi/content/short/2023.05.17.541250v1?rss=1"
Gorin, G.Vastola, J. J.Pachter, L.2023-05-18doi:10.1101/2023.05.17.541250Cold Spring Harbor Laboratory Press2023-05-18
<![CDATA[
CRISPR Screening Uncovers a Long-Range Enhancer for ONECUT1 in Pancreatic Differentiation and Links a Diabetes Risk Variant
]]>
https://biorxiv.org/cgi/content/short/2024.04.26.591412v1?rss=1"
Kaplan, S. J.Wong, W.Yan, J.Pulecio, J.Cho, H.Leslie-Iyer, J.Kazakov, J.Zhao, J.Li, Q.Murphy, D.Luo, R.Dey, K. K.Apostolou, E.Lesie, C. S.Huangfu, D.2024-04-29doi:10.1101/2024.04.26.591412Cold Spring Harbor Laboratory Press2024-04-29
<![CDATA[
Massively parallel reporter assays and mouse transgenic assays provide complementary information about neuronal enhancer activity
]]>
https://biorxiv.org/cgi/content/short/2024.04.22.590634v1?rss=1"
Kosicki, M.Cintron, D. L.Page, N. F.Georgakopoulos-Soares, I.Akiyama, J. A.Plajzer-Frick, I.Novak, C. S.Kato, M.Hunter, R. D.von Maydell, K.Barton, S.Godfrey, P.Beckman, E.Sanders, S. J.Pennacchio, L. A.Ahituv, N.2024-04-23doi:10.1101/2024.04.22.590634Cold Spring Harbor Laboratory Press2024-04-23
<![CDATA[
Massively parallel jumping assay decodes Alu retrotransposition activity
]]>
https://biorxiv.org/cgi/content/short/2024.04.16.589814v1?rss=1"
Ahituv, N.Matharu, N.Zhao, J.Sohota, A.Deng, L.Hung, Y.Li, Z.Sims, J.Rattanasopha, S.Meyer, J.Carbone, L.Kircher, M.2024-04-19doi:10.1101/2024.04.16.589814Cold Spring Harbor Laboratory Press2024-04-19
<![CDATA[
Smooth muscle expression of RNA editing enzyme ADAR1 controls vascular integrity and progression of atherosclerosis
]]>
https://biorxiv.org/cgi/content/short/2024.07.08.602569v1?rss=1"
Weldy, C. S.Li, Q.Monteiro, J. P.Guo, H.Galls, D.Gu, W.Cheng, P. P.Ramste, M.Li, D. Y.Palmisano, B. T.Sharma, D.Worssam, M. D.Zhao, Q.Bhate, A.Kundu, R.Nguyen, T.Li, J. B.Quertermous, T.2024-07-11doi:10.1101/2024.07.08.602569Cold Spring Harbor Laboratory Press2024-07-11
<![CDATA[
Cohesin-mediated 3D contacts tune enhancer-promoter regulation
]]>
https://biorxiv.org/cgi/content/short/2024.07.12.603288v1?rss=1"
50Kb) experiencing much larger changes than proximal ones (e.g., <50Kb). Because most enhancers are located close to their target genes, these observations can explain how only a small subset of genes -- those with strong distal enhancers -- are sensitive to cohesin. Together, our results illuminate how 3D contacts, influenced by both cohesin and genomic distance, tune enhancer effects on gene expression.
]]>Guckelberger, P.Doughty, B. R.Munson, G.Rao, S. S. P.Tan, Y.Cai, X. S.Fulco, C. P.Nasser, J.Mualim, K. S.Bergman, D. T.Ray, J.Jagoda, E.Munger, C. J.Gschwind, A. R.Sheth, M. U.Tan, A. S.Steinmetz, L. M.Lander, E. S.Meissner, A.Lieberman Aiden, E.Engreitz, J. M.2024-07-12doi:10.1101/2024.07.12.603288Cold Spring Harbor Laboratory Press2024-07-12
<![CDATA[
A cell and transcriptome atlas of the human arterial vasculature
]]>
https://biorxiv.org/cgi/content/short/2024.09.10.612293v1?rss=1"
Zhao, Q.Pedroza, A.Sharma, D.Gu, W.Dalal, A.Weldy, C.Jackson, W.Li, D. Y.Ryan, Y.Nguyen, T.Shad, R.Palmisano, B. T.Monteiro, J. P.Worssam, M.Berezwitz, A.Iyer, M.Shi, H.Kundu, R.Limbu, L.Kim, J. B.Kundaje, A.Fischbein, M.Wirka, R.Quertermous, T.Cheng, P.2024-09-10doi:10.1101/2024.09.10.612293Cold Spring Harbor Laboratory Press2024-09-10
<![CDATA[
A missense variant effect map for the human tumour suppressor protein CHK2
]]>
https://biorxiv.org/cgi/content/short/2024.02.13.579700v1?rss=1"
Gebbia, M.Zimmerman, D. I.Jiang, R.Nguyen, M.Weile, J.Li, R.Gavac, M.Kishore, N.Sun, S.Boonen, R. A.Dines, J. N.Wahl, A.Reuter, J.Johnson, B.Fowler, D.van Attikum, H.Roth, F. P.2024-02-15doi:10.1101/2024.02.13.579700Cold Spring Harbor Laboratory Press2024-02-15
<![CDATA[
BIT: Bayesian Identification of Transcriptional Regulators
]]>
https://biorxiv.org/cgi/content/short/2024.06.02.597061v1?rss=1"
Lu, Z.Xu, L.Wang, X.2024-06-03doi:10.1101/2024.06.02.597061Cold Spring Harbor Laboratory Press2024-06-03
<![CDATA[
BayeSMART: Bayesian Clustering of Multi-sample Spatially Resolved Transcriptomics Data
]]>
https://biorxiv.org/cgi/content/short/2024.08.30.610571v1?rss=1"
Guo, Y.Zhu, B.Tang, C.Rong, R.Ma, Y.Xiao, G.Xu, L.Li, Q.2024-09-01doi:10.1101/2024.08.30.610571Cold Spring Harbor Laboratory Press2024-09-01
<![CDATA[
A Regularized Bayesian Dirichlet-multinomial Regression Model for Integrating Single-cell-level Omics and Patient-level Clinical Study Data
]]>
https://biorxiv.org/cgi/content/short/2024.06.04.597391v1?rss=1"
Guo, Y.Yu, L.Guo, L.Xu, L.Li, Q.2024-06-06doi:10.1101/2024.06.04.597391Cold Spring Harbor Laboratory Press2024-06-06
<![CDATA[
Assessing NGS-based computational methods for predicting transcriptional regulators with query gene sets
]]>
https://biorxiv.org/cgi/content/short/2024.02.01.578316v1?rss=1"
Lu, Z.Xiao, X.Zheng, Q.Wang, X.Xu, L.2024-02-06doi:10.1101/2024.02.01.578316Cold Spring Harbor Laboratory Press2024-02-06
<![CDATA[
CRISPR-CLEAR: Nucleotide-Resolution Mapping of Regulatory Elements via Allelic Readout of Tiled Base Editing
]]>
https://biorxiv.org/cgi/content/short/2024.09.09.612085v1?rss=1"
Becerra, B.Wittibschlager, S.Patel, Z. M.Kutschat, A.Delano, J.Karjalainen, A.Wu, T.Starrs, M.Jankowiak, M.Bauer, D.Seruggia, D.Pinello, L.2024-09-09doi:10.1101/2024.09.09.612085Cold Spring Harbor Laboratory Press2024-09-09
<![CDATA[
Characterization and bioinformatic filtering of ambient gRNAs in single-cell CRISPR screens using CLEANSER
]]>
https://biorxiv.org/cgi/content/short/2024.09.04.611293v1?rss=1"
View larger version (66K):
org.highwire.dtl.DTLVardef@165c63dorg.highwire.dtl.DTLVardef@ba0e15org.highwire.dtl.DTLVardef@f2b12eorg.highwire.dtl.DTLVardef@14e6c86_HPS_FORMAT_FIGEXP M_FIG C_FIG
]]>Liu, S.Hamilton, M. C.Cowart, T. N.Barrera, A.Bounds, L. R.Nelson, A. C.Doty, R. W.Allen, A. S.Crawford, G. E.Majoros, W. H.Gersbach, C. A.2024-09-04doi:10.1101/2024.09.04.611293Cold Spring Harbor Laboratory Press2024-09-04
<![CDATA[
scooby: Modeling multi-modal genomic profiles from DNA sequence at single-cell resolution
]]>
https://biorxiv.org/cgi/content/short/2024.09.19.613754v1?rss=1"
Gagneur, J.Hingerl, J. C.Martens, L. D.Manz, T.Theis, F. J.Buenrostro, J. D.Karollus, A.2024-09-22doi:10.1101/2024.09.19.613754Cold Spring Harbor Laboratory Press2024-09-22
<![CDATA[
An integrated, scaled approach to resolve TSC2 variants of uncertain significance
]]>
https://biorxiv.org/cgi/content/short/2026.01.16.699909v1?rss=1"
Biar, C. G.Wang, Z. R.Camp, N. D.Holmes, D. L.Wheelock, M. K.Pendyala, S.McGee, A. V.Gupta, P.McEwen, A. E.Tejura, M.Richardson, M. E.Weyandt, J. D.Coleman, T.Stewart, R.Zeiberg, D.Vandi, A. J.Dawson, S.Radivojac, P.Starita, L. M.Carvill, G. L.James, R. G.Fowler, D. M.Calhoun, J. D.2026-01-18doi:10.64898/2026.01.16.699909Cold Spring Harbor Laboratory Press2026-01-18
<![CDATA[
Uniform processing and analysis of IGVF massively parallel reporter assay data with MPRAsnakeflow
]]>
https://biorxiv.org/cgi/content/short/2025.09.25.678548v1?rss=1"
Rosen, J. D.Vasanthakumari, A. D.Salomon, K.de Lange, N.Dash, P. M.Keukeleire, P.Hassan, A.Barrera, A.Kircher, M.Love, M. I.Schubach, M.2025-09-28doi:10.1101/2025.09.25.678548Cold Spring Harbor Laboratory Press2025-09-28
<![CDATA[
High-throughput biochemical phenotyping of SHP2 variants reveals molecular basis of diseases and allosteric drug inhibition
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https://biorxiv.org/cgi/content/short/2026.03.30.715055v1?rss=1"
300,000 reaction progress curves, we derived kinetic and thermodynamic parameters quantifying variant effects on catalysis, autoinhibition, stability, phosphopeptide binding, and drug responses. This multidimensional dataset reveals that dysregulated autoinhibition, rather than altered stability or catalysis, predominantly determines SHP2-associated pathogenesis. Thermodynamic modeling reveals that clinical-stage allosteric inhibitors preferentially stabilize a previously underappreciated, partially active conformation over the fully inactive state, leading to variant-dependent drug responses. Our high-throughput biochemical framework establishes a general approach to decipher the biochemical logic connecting protein variants to clinical outcomes.
]]>Lee, A. A.Mokhtari, D. A.Egan, E. D.Blacklow, S. C.Herschlag, D.Fordyce, P. M.2026-04-01doi:10.64898/2026.03.30.715055Cold Spring Harbor Laboratory Press2026-04-01
<![CDATA[
Deciphering causal genomic templates of complex molecular phenotypes
]]>
https://biorxiv.org/cgi/content/short/2022.08.15.503769v1?rss=1"
Bhate, S. S.Seigal, A.Caicedo, J.2022-08-15doi:10.1101/2022.08.15.503769Cold Spring Harbor Laboratory Press2022-08-15
<![CDATA[
Simultaneous epigenomic profiling and regulatory activity measurement using e2MPRA
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https://biorxiv.org/cgi/content/short/2025.06.26.661849v1?rss=1"
Zhang, Z.Georgakopoulos Soares, I.Bourque, G.Ahituv, N.Inoue, F.2025-06-30doi:10.1101/2025.06.26.661849Cold Spring Harbor Laboratory Press2025-06-30
<![CDATA[
Large-scale discovery of neural enhancers for cis-regulation therapies
]]>
https://biorxiv.org/cgi/content/short/2025.11.04.686611v1?rss=1"
McDiarmid, T. A.Page, N. F.Chardon, F. M.Daza, R. M.Chen, G. T.Kosicki, M.James, L. M.Nourie, H. C.Laboy-Cintron, D.Lee, A. S.Vij, P.Calderon, D.Lalanne, J.-B.Martin, B. K.Fink, K.Talkowski, M. E.Muotri, A. R.Philpot, B. D.Pennacchio, L. A.Geschwind, D. H.Sanders, S. J.Ahituv, N.Shendure, J.2025-11-05doi:10.1101/2025.11.04.686611Cold Spring Harbor Laboratory Press2025-11-05
<![CDATA[
Capture-C MPRA: A high-throughput method to simultaneously characterize promoter interactions and regulatory activity
]]>
https://biorxiv.org/cgi/content/short/2025.06.11.658967v1?rss=1"
Arnould, C.Keukeleire, P.Inoue, F.Cui, X.An, K.Murray, E.Zhang, X.Drmanac, R.Peters, B.Shendure, J.Shen, Y.Kircher, M.Ahituv, N.2025-06-14doi:10.1101/2025.06.11.658967Cold Spring Harbor Laboratory Press2025-06-14
<![CDATA[
Gene-based calibration of high-throughput functional assays for clinical variant classification
]]>
https://biorxiv.org/cgi/content/short/2025.04.29.651326v1?rss=1"
Zeiberg, D.Tejura, M.McEwen, A. E.Fayer, S.Pejaver, V.Rubin, A. F.Starita, L. M.Fowler, D. M.O'Donnell-Luria, A.Radivojac, P.2025-05-04doi:10.1101/2025.04.29.651326Cold Spring Harbor Laboratory Press2025-05-04
<![CDATA[
Functional evidence for G6PD variant classification from mutational scanning
]]>
https://biorxiv.org/cgi/content/short/2025.08.11.669723v1?rss=1"
Geck, R. C.Wheelock, M. K.Powell, R. L.Wang, Z. R.Holmes, D. L.Fayer, S.Boyle, G. E.Vandi, A. J.Amorosi, C. J.Moore, N.Rubin, A. F.Fowler, D. M.Dunham, M. J.2025-08-14doi:10.1101/2025.08.11.669723Cold Spring Harbor Laboratory Press2025-08-14
<![CDATA[
Gene- and domain-aware calibration increases the clinical utility of variant effect predictors
]]>
https://biorxiv.org/cgi/content/short/2026.02.17.706269v1?rss=1"
Chen, Y.Fayer, S.Jain, S.Benazouz, M.Sverchkov, Y.Stone, J.Sharma, H.Bergquist, T.Stewart, R.Mooney, S. D.Craven, M.Radivojac, P.Starita, L. M.Fowler, D. M.Pejaver, V.2026-02-18doi:10.64898/2026.02.17.706269Cold Spring Harbor Laboratory Press2026-02-18
<![CDATA[
A scalable approach to resolving variants of uncertain significance
]]>
https://biorxiv.org/cgi/content/short/2026.02.14.705848v1?rss=1"
90,000 unobserved variants; 62% had enough evidence to be "preclassified" as pathogenic or benign. We validated our data, evidence and classifications using All of Us and created interactive resources to enable clinical use of the calibrated data. Thus, for 40 genes, representing 1% of the clinical genome, we resolve most existing VUS and future variants, illustrating how systematic use of scalable evidence can empower genomic medicine.
]]>Tejura, M.Chen, Y.McEwen, A. E.Stewart, R.Sverchkov, Y.Laval, F.Woo, I.Zeiberg, D.Shen, R.Fayer, S.Stone, J.Smith, N.Casadei, S.Wang, Z. R.Snyder, M.Capodanno, B. J.Gupta, P.Benazouz, M.Jain, S.Heidl, S.Muffley, L.Dong, S.Lin, K.Hitz, B. C.Gabdank, I.Da, E. Y.Best, S.Grindstaff, S.Reinhart, D.Rodriguez-Salas, L.Seid, O.Vandi, A. J.Wenman, C.Wheelock, M. K.Pendyala, S.Holmes, D.Xu, A.Hosokai, A.Tixhon, M.Reno, C.Ewald, J. D.Spirohn-Fitzgerald, K.Teelucksingh, T.Hao, T.Chen, Z. S.Haghighi, M.Hamid, A. K.2026-02-15doi:10.64898/2026.02.14.705848Cold Spring Harbor Laboratory Press2026-02-15
<![CDATA[
Shared and distinct sequence-function signatures define different modes of human TpoR activation
]]>
https://biorxiv.org/cgi/content/short/2025.09.09.675271v1?rss=1"
Wu, X.McLeod, H.Malinovitch, A.Hunter, S.Ramesh, S.Go, M.Nguyen, J. V.Rubin, A. F.Burger, W. A.Blombery, P.Call, M. E.Call, M. J.2025-09-13doi:10.1101/2025.09.09.675271Cold Spring Harbor Laboratory Press2025-09-13
<![CDATA[
Multiplex, multimodal mapping of variant effects in secreted proteins
]]>
https://biorxiv.org/cgi/content/short/2024.04.01.587474v1?rss=1"
Popp, N. A.Powell, R. L.Wheelock, M. K.Zapp, B. D.Holmes, K. J.Sheldon, K. M.Fletcher, S. N.Wu, X.Fayer, S.Rubin, A. F.Lannert, K. W.Chang, A. T.Sheehan, J. P.Johnsen, J. M.Fowler, D. M.2024-04-01doi:10.1101/2024.04.01.587474Cold Spring Harbor Laboratory Press2024-04-01
<![CDATA[
VEFill: a model for accurate and generalizable deep mutational scanning score imputation across protein domains
]]>
https://biorxiv.org/cgi/content/short/2025.05.14.653991v1?rss=1"
Polunina, P. V.Maier, W.Rubin, A. F.2025-05-14doi:10.1101/2025.05.14.653991Cold Spring Harbor Laboratory Press2025-05-14
<![CDATA[
Genome-scale mapping of variant, enhancer and gene function in primary human CD4+ T cells
]]>
https://biorxiv.org/cgi/content/short/2026.03.09.710372v1?rss=1"
Moonen, D. P.Claringbould, A.Gschwind, A. R.Schrod, S.Braunger, J.Feng, C.Rauscher, B.Yi, J.Bi, S. Z.Matthess, Y.Kaulich, M.Acob, R. A.Ayer, A.Engreitz, J. M.Velten, B.Stegle, O.Trynka, G.Zaugg, J. B.Schraivogel, D.Steinmetz, L. M.2026-03-11doi:10.64898/2026.03.09.710372Cold Spring Harbor Laboratory Press2026-03-11
<![CDATA[
Sensitive, direct detection of non-coding off-target base editor unwinding and editing in primary cells
]]>
https://biorxiv.org/cgi/content/short/2025.09.25.678665v1?rss=1"
460-fold more potential off-target sites than other methods by enriching for Cas9-dependent R-loops immediately preceding editing. Using beCasKAS in primary human T-cells, we observe that mRNA-encoded ABE8e and PAMless ABE8e-SpRY base editors have distinct off-target profiles that can be mitigated by optimizing mRNA dose. Finally, we combine beCasKAS with base-resolution deep learning models to risk-stratify off-target edits by their likelihood of epigenetic dysregulation. Collectively, beCasKAS offers a sensitive and facile tool to optimize the balance between base editor on- and off-target activity.
]]>Wang, T.Jessa, S.Marinov, G. K.Klemm, S.Kundaje, A.Greenleaf, W. J.2025-09-25doi:10.1101/2025.09.25.678665Cold Spring Harbor Laboratory Press2025-09-25
<![CDATA[
An unbiased survey of distal element-gene regulatory interactions with direct-capture targeted Perturb-seq
]]>
https://biorxiv.org/cgi/content/short/2025.09.16.676677v1?rss=1"
Ray, J.Jagoda, E.Sheth, M. U.Galante, J.Amgalan, D.Gschwind, A. R.Munger, C. J.Huang, J.Munson, G.Murphy, M.Mattei, E.Barry, T.Singh, V.Baskaran, A.Kang, H.Katsevich, E.Steinmetz, L. M.Engreitz, J.2025-09-17doi:10.1101/2025.09.16.676677Cold Spring Harbor Laboratory Press2025-09-17
<![CDATA[
An automated ATAC-seq method reveals sequence determinants of transcription factor dose response in the open chromatin
]]>
https://biorxiv.org/cgi/content/short/2025.07.24.666684v1?rss=1"
Liu, B. B.Shimasawa, M.Vermeulen, S.Kim, S. H.Iremadze, N.Lipson, D.Shipony, Z.Greenleaf, W. J.2025-07-27doi:10.1101/2025.07.24.666684Cold Spring Harbor Laboratory Press2025-07-27
<![CDATA[
Vascular smooth muscle cell atherosclerosis trajectories characterized at single cell resolution identify causal transcriptomic and epigenomic mechanisms of disease risk
]]>
https://biorxiv.org/cgi/content/short/2025.06.04.655863v1?rss=1"
Li, D. Y.Kundu, S.Cheng, P.Gu, W.Jackson, W. R.Zhao, Q.Nguyen, T.Worssam, M.Monteiro, J. P.Caceres, R. D.Dale, S.Palmisano, B.Weldy, C. S.Kundu, R.Wirka, R. C.Quertermous, T.2025-06-06doi:10.1101/2025.06.04.655863Cold Spring Harbor Laboratory Press2025-06-06
<![CDATA[
Deep learning the dynamic regulatory sequence code of cardiac organoid differentiation
]]>
https://biorxiv.org/cgi/content/short/2025.10.15.680997v1?rss=1"
Metzl-Raz, E.Zhao, R.Deshpande, S.Powell, J.Porter, E. G.Zouaghi, Y.Liu, B. B.Kim, S. H.Abdi, I.Evergreen, I.Agarwal, M.Sheth, M. U.Rico, J.Miyamoto, M.Sanchez, J. M.Engreitz, J. M.Kundaje, A.Greenleaf, W. J.Gifford, C. A.2025-10-15doi:10.1101/2025.10.15.680997Cold Spring Harbor Laboratory Press2025-10-15
<![CDATA[
Mapping enhancer-gene regulatory interactions from single-cell data
]]>
https://biorxiv.org/cgi/content/short/2024.11.23.624931v1?rss=1"
10,000 evaluated element-gene pairs. We benchmark scE2G models against CRISPR perturbations, fine-mapped eQTLs, and GWAS variant-gene associations and demonstrate state-of-the-art performance at prediction tasks across multiple cell types and categories of perturbations. We apply scE2G to build maps of enhancer-gene regulatory interactions in heterogeneous tissues and interpret noncoding variants associated with complex traits, nominating regulatory interactions linking INPP4B and IL15 to lymphocyte counts. The scE2G models will enable accurate mapping of enhancer-gene regulatory interactions across thousands of diverse human cell types.
]]>Sheth, M. U.Qiu, W.-L.Ma, X. R.Gschwind, A. R.Jagoda, E.Tan, A. S.Einarsson, H.Gorissen, B. L.Dubocanin, D.McGinnis, C. S.Amgalan, D.Satpathy, A. T.Jones, T. R.Steinmetz, L. M.Kundaje, A.Ustun, B.Engreitz, J. M.Andersson, R.2024-11-24doi:10.1101/2024.11.23.624931Cold Spring Harbor Laboratory Press2024-11-24
<![CDATA[
Predicting interaction-specific protein-protein interaction perturbations by missense variants with MutPred-PPI
]]>
https://biorxiv.org/cgi/content/short/2025.12.20.695738v1?rss=1"
Stewart, R.Laval, F.Coppin, G.Spirohn-Fitzgerald, K.Tixhon, M.Hao, T.Calderwood, M. A.Mort, M.Cooper, D. N.Vidal, M.Radivojac, P.2025-12-23doi:10.64898/2025.12.20.695738Cold Spring Harbor Laboratory Press2025-12-23
<![CDATA[
Systematic and proactive evaluation of AIRE missense variant effects
]]>
https://biorxiv.org/cgi/content/short/2025.11.18.688830v1?rss=1"
Axakova, A.Berger, A. H.van Loggerenberg, W.Kishore, N.Gebbia, M.Ding, M. X.Douville, S. V.Tabet, D. R.Cote, A. G.Weile, J.Johansson, S.Bratland, E.Roth, F. P.2025-11-18doi:10.1101/2025.11.18.688830Cold Spring Harbor Laboratory Press2025-11-18
<![CDATA[
Comprehensively Testing the Function of Missense Variation in the STK11 Tumour Suppressor
]]>
https://biorxiv.org/cgi/content/short/2025.07.14.664734v1?rss=1"
Zimmerman, D.Cote, A.van Loggerenberg, W.Gebbia, M.Kishore, N.Weile, J.Li, R.Reno, C.Marsh, A.Hernandez, F.Shahagadkar, P.Grove, L.Meier, S.Wu, H.-J.Fengolia, S.Ahronian, L.Teng, T.Waters, A. J.Seward, D.Taipale, M.Aronson, M.Richardson, M. E.Adams, D.Roth, F.2025-07-18doi:10.1101/2025.07.14.664734Cold Spring Harbor Laboratory Press2025-07-18
<![CDATA[
Landscapes of missense variant impact for human superoxide dismutase 1
]]>
https://biorxiv.org/cgi/content/short/2025.02.25.640191v1?rss=1"
Axakova, A.Ding, M. X.Cote, A. G.Subramaniam, R.Senguttuvan, V.Zhang, H.Weile, J.Douville, S. V.Gebbia, M.Al-Chalabi, A.Wahl, A.Reuter, J.Hurt, J.Mitchell, A.Fradette, S.Andersen, P. M.van Loggerenberg, W.Roth, F. P.2025-02-28doi:10.1101/2025.02.25.640191Cold Spring Harbor Laboratory Press2025-02-28
<![CDATA[
Comprehensive perturbation of transcription factors in human cardiomyocytes reveals the regulatory architecture of congenital heart disease
]]>
https://biorxiv.org/cgi/content/short/2025.12.15.694070v1?rss=1"
50% of CHD remains unexplained. A key challenge is to define the regulatory architecture of CHD genes. Here, we systematically perturb 1983 transcription factors (TFs) during cardiomyocyte differentiation of human stem cells. Our analysis links TFs to gene expression phenotypes across scales and nominates TFs in cardiac cell fate commitment, dosage sensitivity, and transposable element regulation. By deriving TF-gene regulatory networks from experimental perturbation, we gain insights into how developmental networks are structured, use this map to interpret the regulatory architecture of CHD, and deorphanize TFs with roles in CHD that have been under-sampled by genetic studies. To extend these networks to include enhancer-TF-gene linkages, we also perturb 981 putative enhancers of TFs. Finally, we develop a deep learning transformer model to accurately predict perturbed TFs from altered transcriptomes, which we apply to interpret CHD patient transcriptomes. This reference map represents a foundational platform to model the functions of TFs and aids in interpreting CHD variants and mechanisms.
HighlightsO_LISystematic perturbation of 1983 human TFs in cardiac differentiation.
C_LIO_LIDefining the regulatory architecture of CHD genes and cardiac cell fate commitment.
C_LIO_LINominating TFs in dosage sensitivity and regulation of transposable elements.
C_LIO_LIExtended enhancer-TF-gene networks improve fine mapping of patient-derived variants.
C_LIO_LIPerturbation models nominate TFs driving altered regulatory networks in patients.
C_LI
]]>Takeuchi, C.Sivakumar, S.Sundarrajan, A.Wang, Y.Goetsch, S. C.Zhao, H.Wang, L.Nzima, M.Deng, M.Kulkarni, K. N.Xu, L.Wu, J.Posner, B. A.Chahrour, M. H.Kraus, W. L.Munshi, N. V.Hon, G. C.2025-12-17doi:10.64898/2025.12.15.694070Cold Spring Harbor Laboratory Press2025-12-17
<![CDATA[
3D reconstruction of spatial transcriptomics with spatial pattern enhanced graph convolutional neural network
]]>
https://biorxiv.org/cgi/content/short/2026.01.13.699328v1?rss=1"
Tang, C.Zhou, Y.Xiao, X.Dong, L.Yu, L.Li, Q.Xiao, G.Xu, L.2026-01-14doi:10.64898/2026.01.13.699328Cold Spring Harbor Laboratory Press2026-01-14
<![CDATA[
SpaFun: Discovering Domain-specific Spatial Expression Patterns and New Disease-Relevant Genes using Functional Principal Component Analysis
]]>
https://biorxiv.org/cgi/content/short/2025.02.17.638766v1?rss=1"
Jiang, X.Guo, Y.Guo, L.Zhong, L.Wang, J.Xiao, G.Li, Q.Xu, L.2025-02-21doi:10.1101/2025.02.17.638766Cold Spring Harbor Laboratory Press2025-02-21
<![CDATA[
Benchmarking and optimizing Perturb-seq in differentiating human pluripotent stem cells
]]>
https://biorxiv.org/cgi/content/short/2025.01.21.633969v1?rss=1"
Sivakumar, S.Wang, Y.Goetsch, S. C.Pandit, V.Wang, L.Zhao, H.Sundarrajan, A.Armendariz, D. A.Takeuchi, C.Nzima, M.Chen, W.-C.Dederich, A. E.El Hayek, L.Gao, T.Ghazawi, R.Gogate, A.Kaur, K.Kim, H. B.McCoy, M.Niederstrasser, H.Oura, S.Pinzon-Arteaga, C. A.Sanghvi, M.Schmitz, D. A.Yu, L.Zhang, Y.Zhou, Q.Kraus, W. L.Xu, L.Wu, J.Posner, B. A.Chahrour, M. H.Hon, G. C.Munshi, N. V.2025-01-23doi:10.1101/2025.01.21.633969Cold Spring Harbor Laboratory Press2025-01-23
<![CDATA[
Reprogramming of neuronal genome function and phenotype by astrocytes
]]>
https://biorxiv.org/cgi/content/short/2026.03.07.710282v1?rss=1"
200 astrocyte-responsive TF genes uncovered discrete functional clusters that promote neuronal maturity or stemness
C_LIO_LIAstrocyte-responsive TF genes reprogram neuronal electrophysiology and neurite morphology
C_LI
]]>Li, B.Hagy, K.Safi, A.Beer, M. A.Barrera, A.Geraghty, S.Rai, R.Pederson, A. N.Reisman, S. J.Love, M. I.Sullivan, P. F.Eroglu, C.Crawford, G. E.Gersbach, C. A.2026-03-07doi:10.64898/2026.03.07.710282Cold Spring Harbor Laboratory Press2026-03-07
<![CDATA[
Functional Annotation of the Major Histocompatibility Complex Locus
]]>
https://biorxiv.org/cgi/content/short/2026.02.01.703124v1?rss=1"
Bounds, L. R.Barrera, A.ter Weele, M.Liu, S.Wu, E.Li, S.Venukuttan, R.Rai, R.Mu, W.Iglesias, N.Giusti-Rodriguez, P.Reddy, T. E.Li, Y.Gordan, R.Allen, A. S.Love, M. I.Sullivan, P. F.Crawford, G. E.Gersbach, C. A.2026-02-03doi:10.64898/2026.02.01.703124Cold Spring Harbor Laboratory Press2026-02-03
<![CDATA[
Higher eQTL power reveals signals that boost GWAS colocalization
]]>
https://biorxiv.org/cgi/content/short/2025.08.05.668745v1?rss=1"
Rosen, J. D.Broadaway, K. A.Brotman, S. M.Mohlke, K. L.Love, M. I.2025-08-05doi:10.1101/2025.08.05.668745Cold Spring Harbor Laboratory Press2025-08-05
<![CDATA[
Structured Pooling Improves Detection of Rare Regulatory Mutations in Population-Scale Reporter Assays
]]>
https://biorxiv.org/cgi/content/short/2026.03.27.714794v1?rss=1"
Dura, K.Siklenka, K.Strouse, K. P.Morrow, S.Zhang, C.Barrera, A.Allen, A. S.Reddy, T. E.Majoros, W. H.2026-03-31doi:10.64898/2026.03.27.714794Cold Spring Harbor Laboratory Press2026-03-31
<![CDATA[
Modeling gene regulatory perturbations via deep learning from high-throughput reporter assays
]]>
https://biorxiv.org/cgi/content/short/2026.03.27.714770v1?rss=1"
Venukuttan, R.Doty, R.Thomson, A.Chen, Y.Li, B.Duan, Y.Barrera, A.Dura, K.Ko, K.-Y.Lapp, H.Reddy, T. E.Allen, A. S.Majoros, W. H.2026-03-31doi:10.64898/2026.03.27.714770Cold Spring Harbor Laboratory Press2026-03-31
<![CDATA[
Mismatch tolerance of a gRNA for CRISPR-based gene activation confers broad activity critical for cell reprogramming
]]>
https://biorxiv.org/cgi/content/short/2026.02.01.703129v1?rss=1"
View larger version (34K):
org.highwire.dtl.DTLVardef@b697b0org.highwire.dtl.DTLVardef@1a0b390org.highwire.dtl.DTLVardef@16ce710org.highwire.dtl.DTLVardef@b5d87a_HPS_FORMAT_FIGEXP M_FIG C_FIG
]]>Reisman, S. J.Zhu, W.Miller, S. E.Halabi, D.Sangvai, N.Crawford, G. E.Gordan, R.Gersbach, C. A.2026-02-03doi:10.64898/2026.02.01.703129Cold Spring Harbor Laboratory Press2026-02-03
<![CDATA[
Comprehensive profiling of transcription factors for reprogramming human astrocytes to neuronal cells through endogenous CRISPR-based gene activation
]]>
https://biorxiv.org/cgi/content/short/2025.10.11.681828v1?rss=1"
Reisman, S. J.Halabi, D.Miller, S. E.Song, L.Geraghty, S.Sangvai, N.Rice, G.Safi, A.Crawford, G. E.Gersbach, C. A.2025-10-12doi:10.1101/2025.10.11.681828Cold Spring Harbor Laboratory Press2025-10-12
<![CDATA[
RELB Reprograms Exhausted Tumor-Infiltrating Lymphocytes for Improved Adoptive Cell Therapy
]]>
https://biorxiv.org/cgi/content/short/2025.10.11.681829v1?rss=1"
McRoberts Amador, C. D.Conover, R. E.Brown, M. C.Lyniv, L. S.Noldner, P. K.Zhou, Y.Gao, A. R.McCutcheon, S. R.Antonia, S. J.Gersbach, C. A.2025-10-12doi:10.1101/2025.10.11.681829Cold Spring Harbor Laboratory Press2025-10-12
<![CDATA[
A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
]]>
https://biorxiv.org/cgi/content/short/2025.07.19.665672v1?rss=1"
Anglen, T.Kaplow, I. M.Choi, B.Dewars, E.Perelli, R. M.Hagy, K. T.Tran, D.Ramaker, M. E.Shah, S.Jung, I.Landstrom, A. P.Karra, R.Diao, Y.Gersbach, C. A.2025-07-20doi:10.1101/2025.07.19.665672Cold Spring Harbor Laboratory Press2025-07-20
<![CDATA[
Genome-wide annotation of gene regulatory elements linked to cell fitness
]]>
https://biorxiv.org/cgi/content/short/2021.03.08.434470v1?rss=1"
Klann, T.Barrera, A.Ettyreddy, A.Rickels, R.Bryois, J.Jiang, S.Adkar, S.Iglesias, N.Sullivan, P.Reddy, T. E.Crawford, G. E.Gersbach, C.2021-03-09doi:10.1101/2021.03.08.434470Cold Spring Harbor Laboratory Press2021-03-09
<![CDATA[
Cell modeling and rescue of a novel non-coding genetic cause of Glycogen Storage Disease IX
]]>
https://biorxiv.org/cgi/content/short/2025.05.14.654043v1?rss=1"
Iyengar, A. K.Zou, X.Dai, J.Francis, R. A.Safi, A.Patterson, K.Koch, R. L.Clarke, S.Beaman, M. M.Chong, J. X.Bamshad, M. J.Majoros, W. H.Rehder, R. C.Bali, D. S.Allen, A. S.Crawford, G. E.Kishnani, P. S.Reddy, T. E.2025-05-17doi:10.1101/2025.05.14.654043Cold Spring Harbor Laboratory Press2025-05-17
<![CDATA[
Enhancer-driven regulatory network of forebrain human development provides insights into autism
]]>
https://biorxiv.org/cgi/content/short/2023.09.06.555206v1?rss=1"
Vaccarino, F. M.Jourdon, A.Mariani, J.Wu, F.Capauto, D.Norton, S.Tomasini, L.Amiri, A.Schreiner, J.Nguyen, C. K.Nolan, N.Szekely, A.McPartland, J. C.Pelphrey, K.Chawarska, K.Ventola, P.Abyzov, A.2023-09-08doi:10.1101/2023.09.06.555206Cold Spring Harbor Laboratory Press2023-09-08
<![CDATA[
Clonal memory of colitis accumulates and promotes tumor growth
]]>
https://biorxiv.org/cgi/content/short/2025.02.13.638099v1?rss=1"
Nagaraja, S.Ojeda-Miron, L.Zhang, R.Oreskovic, E.Hu, Y.Zeve, D.Sharma, K.Hyman, R. R.Zhang, Q.Castillo, A.Breault, D. T.Yilmaz, O. H.Buenrostro, J. D.2025-02-17doi:10.1101/2025.02.13.638099Cold Spring Harbor Laboratory Press2025-02-17
<![CDATA[
Comparing bulk and single-cell methodologies and models to profile gene expression, chromatin accessibility and regulatory links in endothelial cells treated with TNFα
]]>
https://biorxiv.org/cgi/content/short/2026.03.13.711357v1?rss=1"
Zevounou, J.Lo, K. S.McGinnis, C. S.Satpathy, A. T.Lettre, G.2026-03-16doi:10.64898/2026.03.13.711357Cold Spring Harbor Laboratory Press2026-03-16
<![CDATA[
Massive-scale single-nucleus multi-omics identifies novel rare noncoding drivers of Parkinson's disease
]]>
https://biorxiv.org/cgi/content/short/2026.03.05.709922v1?rss=1"
3.3 million nuclei sampled from five brain regions across a cohort of 80 individuals with Parkinsons disease (PD) and 21 neurologically normal control individuals with matched 30x whole-genome sequencing. We use this data to identify cell type-specific features of PD, map cell type-specific chromatin accessibility and expression quantitative trait loci, and train machine learning models to predict the effect of variants on gene regulation. We identify rare noncoding variants statistically associated with sporadic PD and extend our approaches to predict drivers of familial PD of unknown genetic origin. Our results underscore the significance of rare noncoding variants in complex diseases and provide a roadmap for applying similar approaches in other disease systems.
]]>Menon, S.Turner, A. W.Chang, S. H.Johnson, A. W.Chang, H. H.Shah, A. J.Zeng, Y.Strohlein, C. E.Kampman, L.Colston, C.Kozlenkov, A.Dracheva, S.Avenali, M.Palermo, G.Ceravolo, R.Valente, E. M.Gabbert, C.Trinh, J.Serrano, G. E.Beach, T. G.Global Parkinson's Genetic Program (GP2),Shulman, J. M.Blauwendraat, C.Montine, T. J.Fang, Z.-H.Belloy, M. E.Corces, M. R.2026-03-05doi:10.64898/2026.03.05.709922Cold Spring Harbor Laboratory Press2026-03-05
<![CDATA[
Base-editing a single missense mutation in A20 enhances CAR-T cell efficacy
]]>
https://biorxiv.org/cgi/content/short/2025.10.05.680562v1?rss=1"
Blaisdell, A.Bachl, S.Sandoval, L. R.Ching, C.Bowman, C. J.Kale, N.Prabandham, M.Diolaiti, M.Havig, C.Advincula, R.Lenci, N.Li, Z.Yamashita, E.Wang, C. H.Zhang, S.Liu, Q.Achacoso, P.Stibor, D.Oynebraten, I.Seo, J.Ashworth, A.Marson, A.Ye, C. J.Malynn, B. A.Eyquem, J.Carnevale, J.Ma, A.2025-10-06doi:10.1101/2025.10.05.680562Cold Spring Harbor Laboratory Press2025-10-06
<![CDATA[
Cryo-mtscATAC-seq for single-cell mitochondrial DNA genotyping and clonal tracing in archived human tissues
]]>
https://biorxiv.org/cgi/content/short/2025.09.17.675534v1?rss=1"
Salla, M.Obermayer, B.Cotta, M.Friebel, E.Campo-Garcia, J.Charalambous, G.Bueno, R. J.Lieu, D.Dabek, P.Helmuth, A.Tellides, G.Assi, R.Bankov, K.Lodrini, M.Deubzer, H.Chung, H.Beule, D.Radbruch, H.Capper, D.Heppner, F.Starossom, S. C.Lareau, C.Liu, I.Ludwig, L. S.2025-09-20doi:10.1101/2025.09.17.675534Cold Spring Harbor Laboratory Press2025-09-20
<![CDATA[
Defining the host dependencies and the transcriptional landscape of RSV infection and bystander activation
]]>
https://biorxiv.org/cgi/content/short/2025.03.26.645108v1?rss=1"
Sunshine, S.Puschnik, A.Retallack, H.Laurie, M. T.Liu, J.Peng, D.Knopp, K.Zinter, M. S.Ye, C. J.DeRisi, J. L.2025-03-26doi:10.1101/2025.03.26.645108Cold Spring Harbor Laboratory Press2025-03-26
<![CDATA[
Clonal lineage tracing of innate immune cells in human cancer
]]>
https://biorxiv.org/cgi/content/short/2025.07.16.665245v1?rss=1"
Liu, V.Sandor, K.Yan, P. K.Miao, M.Yin, Y.Stickels, R. R.Chen, A. Y.Hiam-Galvez, K.Gutierrez, J.Zhang, W.Sajjath, S. M.Valbuena, R.Wang, S.Daniel, B.Ludwig, L. S.Howitt, B. E.Lareau, C. A.Satpathy, A. T.2025-07-21doi:10.1101/2025.07.16.665245Cold Spring Harbor Laboratory Press2025-07-21
<![CDATA[
Cell cycle-coupled transcriptional network orchestrates human B cell fate bifurcation
]]>
https://biorxiv.org/cgi/content/short/2025.04.23.649973v1?rss=1"
Pease, N. A.Fan, J.Keshari, S.Stratton, J.Gerges, P.Ann Varghese, B.Nampoothiri VP, N.McGinnnis, C. S.Zhang, W.Geirlack, S. B.Swaminathan, T.Sachan, A.Manakkat Vijay, G.Mena Hernandez, L.Heidari Rarani, Z.Macedo, C.Metes, D.Satpathy, A. T.Jain, A. K.Sahni, N.Stallaert, W.Das, J.Singh, H.2025-04-24doi:10.1101/2025.04.23.649973Cold Spring Harbor Laboratory Press2025-04-24
<![CDATA[
Transcript-specific enrichment enables profiling rare cell states via scRNA-seq
]]>
https://biorxiv.org/cgi/content/short/2024.03.27.587039v1?rss=1"
Abay, T.Stickels, R. R.Takizawa, M. T.Nalbant, B. N.Hsieh, Y.-H.Hwang, S.Snopkowski, C.Yu, K. K. H.Abou-Mrad, Z.Tabar, V.Ludwig, L. S.Chaligne, R.Satpathy, A. T.Lareau, C. A.2024-03-27doi:10.1101/2024.03.27.587039Cold Spring Harbor Laboratory Press2024-03-27
<![CDATA[
Hybrid crosses reveal a cell-type-specific landscape of mouse regulatory variation
]]>
https://biorxiv.org/cgi/content/short/2026.04.02.716195v1?rss=1"
Weber, R.Carilli, M.Rebboah, E.Filimban, G.Liang, H. Y.Trout, D.Duffield, M.Mahdipoor, P.Taghizadeh, E.Fattahi, N.Mojaverzargar, R.Kawauchi, S.Williams, B. A.MacGregor, G.Wold, B.Pachter, L.Hallgrimsdottir, I. B.Mortazavi, A.2026-04-04doi:10.64898/2026.04.02.716195Cold Spring Harbor Laboratory Press2026-04-04
<![CDATA[
Single-Cell Genomics Decontamination with CellSweep
]]>
https://biorxiv.org/cgi/content/short/2026.03.04.709349v1?rss=1"
Caskey, M.Rich, J.Weber, R.Mortazavi, A.Pachter, L.Hallgrimsdottir, I. B.2026-03-06doi:10.64898/2026.03.04.709349Cold Spring Harbor Laboratory Press2026-03-06
<![CDATA[
Estimating cis and trans contributions todifferences in gene regulation
]]>
https://biorxiv.org/cgi/content/short/2024.07.13.603403v1?rss=1"
Hallgrimsdottir, I. B.Carilli, M.Pachter, L.2024-07-16doi:10.1101/2024.07.13.603403Cold Spring Harbor Laboratory Press2024-07-16
<![CDATA[
Determining gene specificity from multivariate single-cell RNA sequencing data
]]>
https://biorxiv.org/cgi/content/short/2025.11.21.689845v1?rss=1"
Swarna, N. P.Booeshaghi, A. S.Rebboah, E.Gordon, M. G.Kathail, P.Li, T.Alvarez, M.Ye, C. J.Wold, B. J.Mortazavi, A.Pachter, L.2025-11-24doi:10.1101/2025.11.21.689845Cold Spring Harbor Laboratory Press2025-11-24
<![CDATA[
Quantitative assessment of single-cell RNA-seq clustering with CONCORDEX
]]>
https://biorxiv.org/cgi/content/short/2023.06.28.546949v1?rss=1"
Jackson, K. C.Booeshaghi, A. S.Galvez-Merchan, A.Moses, L.Chari, T.Pachter, L.2023-06-30doi:10.1101/2023.06.28.546949Cold Spring Harbor Laboratory Press2023-06-30
<![CDATA[
Dogme: A nextflow pipeline for reprocessing nanopore RNA and DNA modifications
]]>
https://biorxiv.org/cgi/content/short/2025.06.04.657941v1?rss=1"
Abdollahzadeh, E.Mortazavi, A.2025-06-08doi:10.1101/2025.06.04.657941Cold Spring Harbor Laboratory Press2025-06-08
<![CDATA[
Pseudoassembly of k-mers
]]>
https://biorxiv.org/cgi/content/short/2025.05.11.653354v1?rss=1"
Sullivan, D. K.Boffelli, M.Pachter, L.2025-05-13doi:10.1101/2025.05.11.653354Cold Spring Harbor Laboratory Press2025-05-13
<![CDATA[
Systematic cell-type resolved transcriptomes of 8 tissues in 8 lab and wild-derived mouse strains captures global and local expression variation
]]>
https://biorxiv.org/cgi/content/short/2025.04.21.649844v1?rss=1"
Rebboah, E.Weber, R.Abdollahzadeh, E.Swarna, N. P.Sullivan, D. K.Trout, D.Reese, F.Liang, H. Y.Filimban, G.Mahdipour, P.Duffield, M.Mojaverzargar, R.Taghizadeh, E.Fattahi, N.Mojgani, N.Zhang, H.Loving, R. K.Carilli, M.Booeshaghi, A. S.Kawauchi, S.Hallgrimsdottir, I. B.Williams, B. A.MacGregor, G.Pachter, L.Wold, B.Mortazavi, A.2025-04-24doi:10.1101/2025.04.21.649844Cold Spring Harbor Laboratory Press2025-04-24
<![CDATA[
Geospatially informed representation of spatial genomics data with SpatialFeatureExperiment
]]>
https://biorxiv.org/cgi/content/short/2025.02.24.640007v1?rss=1"
Moses, L.Huseynov, A.Rich, J.Pachter, L.2025-02-27doi:10.1101/2025.02.24.640007Cold Spring Harbor Laboratory Press2025-02-27
<![CDATA[
Long-read sequencing transcriptome quantification with lr-kallisto
]]>
https://biorxiv.org/cgi/content/short/2024.07.19.604364v1?rss=1"
Loving, R. K.Sullivan, D. K.Reese, F.Rebboah, E.Sakr, J.Rezaie, N.Liang, H. Y.Filimban, G.Kawauchi, S.Oakes, C.Trout, D.Williams, B. A.MacGregor, G.Wold, B.Mortazavi, A.Pachter, L.2024-07-19doi:10.1101/2024.07.19.604364Cold Spring Harbor Laboratory Press2024-07-19
<![CDATA[
Stochastic Modeling of Biophysical Responses to Perturbation
]]>
https://biorxiv.org/cgi/content/short/2024.07.04.602131v1?rss=1"
Chari, T.Gorin, G.Pachter, L.2024-07-06doi:10.1101/2024.07.04.602131Cold Spring Harbor Laboratory Press2024-07-06
<![CDATA[
The impact of package selection and versioning on single-cell RNA-seq analysis
]]>
https://biorxiv.org/cgi/content/short/2024.04.04.588111v1?rss=1"
Rich, J. M.Moses, L.Einarsson, P. H.Jackson, K.Luebbert, L.Booeshaghi, A. S.Antonsson, S.Sullivan, D. K.Bray, N.Melsted, P.Pachter, L.2024-04-05doi:10.1101/2024.04.04.588111Cold Spring Harbor Laboratory Press2024-04-05
<![CDATA[
Accurate quantification of single-nucleus and single-cell RNA-seq transcripts
]]>
https://biorxiv.org/cgi/content/short/2022.12.02.518832v1?rss=1"
Eldjarn Hjörleifsson, K.Sullivan, D. K.Holley, G.Melsted, P.Pachter, L.2022-12-02doi:10.1101/2022.12.02.518832Cold Spring Harbor Laboratory Press2022-12-02
<![CDATA[
Organ-specific prioritization and annotation of non-coding regulatory variants in the human genome
]]>
https://biorxiv.org/cgi/content/short/2023.09.07.556700v1?rss=1"
Zhao, N.Dong, S.Boyle, A. P.2023-09-08doi:10.1101/2023.09.07.556700Cold Spring Harbor Laboratory Press2023-09-08
<![CDATA[
Long-term Reprogramming and Altered Ontogeny of Classical Monocytes Mediates Enhanced Lung Injury in Sepsis Survivor Mice
]]>
https://biorxiv.org/cgi/content/short/2025.05.16.654442v1?rss=1"
Denstaedt, S. J.McBean, B.Boyle, A. P.Arenberg, B. C.Mack, M.Moore, B. B.Newstead, M. W.Singer, B. H.Cano, J.Prescott, H. C.Goodridge, H. S.Zemans, R. L.2025-05-21doi:10.1101/2025.05.16.654442Cold Spring Harbor Laboratory Press2025-05-21
<![CDATA[
Developing a general AI model for integrating diverse genomic modalities and comprehensive genomic knowledge
]]>
https://biorxiv.org/cgi/content/short/2025.05.08.652986v1?rss=1"
Zhang, Z.Bao, X.Jiang, L.Luo, X.Wang, Y.Comai, A.Waldhaus, J.Hansen, A. S.Li, W.Liu, J.2025-05-14doi:10.1101/2025.05.08.652986Cold Spring Harbor Laboratory Press2025-05-14
<![CDATA[
Enhancing Portability of Trans-Ancestral Polygenic Risk Scores through Tissue-Specific Functional Genomic Data Integration
]]>
https://biorxiv.org/cgi/content/short/2024.02.07.579365v1?rss=1"
Crone, B.Boyle, A. P.2024-02-09doi:10.1101/2024.02.07.579365Cold Spring Harbor Laboratory Press2024-02-09
<![CDATA[
Federated single-cell QTL meta-analysis reveals novel disease mechanisms
]]>
https://biorxiv.org/cgi/content/short/2026.01.20.700519v1?rss=1"
Kaptijn, D.Michielsen, L.Neavin, D.Ripoll-Cladellas, A.Alquicira-Hernandez, J. E.Korshevniuk, M.Lee, J. T. H.Oelen, R.Vochteloo, M.Warmerdam, R.Ando, Y.Ban, M.Bayaraa, O.Berg, M.van Blokland, I.Considine, D.Dieng, M. M.Edahiro, R.Gordon, M. G.Groot, H. E.van der Harst, P.Heinig, M.Hon, C.-C.Idaghdour, Y.Kathail, P.de Klein, N.Li, W.Li, Y.Losert, C.Manikanda, V.Moody, J.Naeem, H.Mokrab, Y.Nawijn, M. C.Netea, M.Niewold, J.Okada, Y.Sawcer, S.Soulama, I.Stegle, O.Tsepilov, Y.Park, W.-Y.Rajagopalan, D.Shahin, T.2026-01-23doi:10.64898/2026.01.20.700519Cold Spring Harbor Laboratory Press2026-01-23
<![CDATA[
Farm animal evolution demonstrates hidden molecular basis of human traits
]]>
https://biorxiv.org/cgi/content/short/2026.02.02.703413v1?rss=1"
Connally, N. J.Sunyaev, S.2026-02-04doi:10.64898/2026.02.02.703413Cold Spring Harbor Laboratory Press2026-02-04
<![CDATA[
Cellular and Regional Vulnerability Shapes the Molecular Landscape of Psychosis in Alzheimers Disease
]]>
https://biorxiv.org/cgi/content/short/2025.04.30.651435v1?rss=1"
Victor, M. B.Sun, N.Galani, K.Leary, N.Tanigawa, Y.Scannail, A. N.Ho, L.-L.Prosper, S.Liu, L.Kofler, J. K.Sweet, R.Tsai, L.-H.Kellis, M.2025-05-07doi:10.1101/2025.04.30.651435Cold Spring Harbor Laboratory Press2025-05-07
<![CDATA[
NERINE reveals rare variant associations in gene networks across multiple phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson's disease
]]>
https://biorxiv.org/cgi/content/short/2025.01.07.631688v1?rss=1"
Nazeen, S.Wang, X.Morrow, A.Strom, R.Ethier, E.Ritter, D.Henderson, A.Afroz, J.Stitziel, N. O.Gupta, R. M.Luk, K.Studer, L.Khurana, V.Sunyaev, S. R.2025-01-10doi:10.1101/2025.01.07.631688Cold Spring Harbor Laboratory Press2025-01-10
<![CDATA[
Inherent instability of simple DNA repeats shapes an evolutionarily stable distribution of repeat lengths
]]>
https://biorxiv.org/cgi/content/short/2025.01.09.631797v1?rss=1"
McGinty, R. J.Balick, D. J.Mirkin, S. M.Sunyaev, S. R.2025-01-10doi:10.1101/2025.01.09.631797Cold Spring Harbor Laboratory Press2025-01-10
<![CDATA[
Segregating DNA lesions point to high selective advantage of tumor initiating cells
]]>
https://biorxiv.org/cgi/content/short/2025.10.02.680094v1?rss=1"
Seplyarskiy, V.Shady, M.Andrianova, M. A.Chapman, M. S.Van Allen, E.Sunyaev, S. R.2025-10-04doi:10.1101/2025.10.02.680094Cold Spring Harbor Laboratory Press2025-10-04
<![CDATA[
Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases
]]>
https://biorxiv.org/cgi/content/short/2025.09.23.677874v1?rss=1"
Koh, B.Gal Oz, S. T.Sato, R.Nguyen, H.Dunlap, G. S.Mahony, C.Bolton, C.Wedderburn, L. R.Croft, A.Donlin, L.Raychaudhuri, S.Korsunskiy, I.Rao, D. A.Brenner, M. B.2025-09-25doi:10.1101/2025.09.23.677874Cold Spring Harbor Laboratory Press2025-09-25
<![CDATA[
TCR germline diversity reveals evidence of natural selection on variable and joining alpha chain genes
]]>
https://biorxiv.org/cgi/content/short/2025.08.20.671277v1?rss=1"
Mantena, S.Akbari, A.Raychaudhuri, S.2025-08-24doi:10.1101/2025.08.20.671277Cold Spring Harbor Laboratory Press2025-08-24
<![CDATA[
Defining effective strategies to integrate multi-sample single-nucleus ATAC-seq datasets via a multimodal-guided approach
]]>
https://biorxiv.org/cgi/content/short/2025.04.02.646871v1?rss=1"
Weinand, K.Langan, E. M.Curtis, M.Raychaudhuri, S.2025-04-03doi:10.1101/2025.04.02.646871Cold Spring Harbor Laboratory Press2025-04-03
<![CDATA[
Early and late RNA eQTL are driven by different genetic mechanisms
]]>
https://biorxiv.org/cgi/content/short/2025.02.24.639351v1?rss=1"
Sakaue, S.Accelerating Medicines Partnership: RA/SLE Network,Raychaudhuri, S.2025-02-26doi:10.1101/2025.02.24.639351Cold Spring Harbor Laboratory Press2025-02-26
<![CDATA[
Wnt signaling drives stromal inflammation in inflammatory arthritis
]]>
https://biorxiv.org/cgi/content/short/2025.01.06.631510v1?rss=1"
Mueller, A. A.Zou, A. E.Marsh, L.-J.Kemble, S.Nayar, S.Watts, G. F. M.Murphy, C. L.Taylor, E.Major, T.Gardner, D.Buckley, C. D.Wei, K.Raychaudhuri, S.Korsunsky, I.Filer, A.Croft, A. P.Brenner, M. B.2025-01-08doi:10.1101/2025.01.06.631510Cold Spring Harbor Laboratory Press2025-01-08
<![CDATA[
Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations
]]>
https://biorxiv.org/cgi/content/short/2024.02.13.580158v1?rss=1"
Kobren, S. N.Moldovan, M. A.Reimers, R.Traviglia, D.Li, X.Barnum, D.Veit, A.Willett, J.Berselli, M.Ronchetti, W.Sherwood, R.Krier, J.Kohane, I. S.Undiagnosed Diseases Network,Sunyaev, S. R.2024-02-16doi:10.1101/2024.02.13.580158Cold Spring Harbor Laboratory Press2024-02-16
<![CDATA[
Reproducible single cell annotation of programs underlying T-cell subsets, activation states, and functions
]]>
https://biorxiv.org/cgi/content/short/2024.05.03.592310v1?rss=1"
Kotliar, D.Curtis, M.Agnew, R.Weinand, K.Nathan, A.Baglaenko, Y.Zhao, Y.Sabeti, P. C.Rao, D. A.Raychaudhuri, S.2024-05-05doi:10.1101/2024.05.03.592310Cold Spring Harbor Laboratory Press2024-05-05
<![CDATA[
Modeling heterogeneity in single-cell perturbation states enhances detection of response eQTLs
]]>
https://biorxiv.org/cgi/content/short/2024.02.20.581100v1?rss=1"
Raychaudhuri, S.Valencia, C.Nathan, A.Kang, J. B.Rumker, L.Lee, H.2024-02-22doi:10.1101/2024.02.20.581100Cold Spring Harbor Laboratory Press2024-02-22
<![CDATA[
Ancestry-specific performance of variant effect predictors in clinical variant classification
]]>
https://biorxiv.org/cgi/content/short/2026.02.14.705914v1?rss=1"
Hoffing, R.Zeiberg, D.Stenton, S. L.Mort, M.Cooper, D. N.Hahn, M. W.O'Donnell-Luria, A.Ward, L. D.Radivojac, P.2026-02-17doi:10.64898/2026.02.14.705914Cold Spring Harbor Laboratory Press2026-02-17
<![CDATA[
Calibration of additional computational tools expands ClinGen recommendation options for variant classification with PP3/BP4 criteria
]]>
https://biorxiv.org/cgi/content/short/2024.09.17.611902v1?rss=1"
Bergquist, T.Stenton, S. L.Nadeau, E. A. W.Byrne, A. B.Greenblatt, M. S.Harrison, S. M.Tavtigian, S. V.O'Donnell-Luria, A.Biesecker, L. G.Radivojac, P.Brenner, S. E.Pejaver, V.ClinGen Sequence Variant Interpretation Working Group,2024-09-21doi:10.1101/2024.09.17.611902Cold Spring Harbor Laboratory Press2024-09-21
<![CDATA[
Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A
]]>
https://biorxiv.org/cgi/content/short/2024.05.16.594558v1?rss=1"
Jain, S.Trinidad, M.Nguyen, T. B.Jones, K.Diaz Neto, S.Ge, F.Glagovsky, A.Jones, C.Moran, G.Wang, B.Rahimi, K.Zeynep Calici, S.Cedillo, L. R.Berardelli, S.Ozden, B.Chen, K.Katsonis, P.Williams, A.Lichtarge, O.Rana, S.Pradhan, S.Srinivasan, R.Sajeed, R.Joshi, D.Faraggi, E.Jernigan, R.Kloczkowski, A.Xu, J.Song, Z.Ozkan, S.Padilla, N.de la Cruz, X.Acuna-Hidalgo, R.Grafmuller, A.Jimenez Barron, L. T.Manfredi, M.Savojardo, C.Babbi, G.Martelli, P. L.Casadio, R.Sun, Y.Zhu, S.Shen, Y.Pucci, F.Rooman, M.Cia, G.R2024-05-19doi:10.1101/2024.05.16.594558Cold Spring Harbor Laboratory Press2024-05-19
<![CDATA[
Critical assessment of missense variant effect predictors on disease-relevant variant data
]]>
https://biorxiv.org/cgi/content/short/2024.06.06.597828v1?rss=1"
Rastogi, R.Chung, R.Li, S.Li, C.Lee, K.Woo, J.Kim, D.-W.Keum, C.Babbi, G.Martelli, P. L.Savojardo, C.Casadio, R.Chennen, K.Weber, T.Poch, O.Ancien, F.Cia, G.Pucci, F.Raimondi, D.Vranken, W.Rooman, M.Marquet, C.Olenyi, T.Rost, B.Andreoletti, G.Kamandula, A.Peng, Y.Bakolitsa, C.Mort, M.Cooper, D. N.Bergquist, T.Pejaver, V.Liu, X.Radivojac, P.Brenner, S. E.Ioannidis, N. M.2024-06-08doi:10.1101/2024.06.06.597828Cold Spring Harbor Laboratory Press2024-06-08
<![CDATA[
The landscape of regional missense mutational intolerance quantified from 125,748 exomes
]]>
https://biorxiv.org/cgi/content/short/2024.04.11.588920v1?rss=1"
Chao, K. R.Wang, L.Panchal, R.Liao, C.Abderrazzaq, H.Ye, R.Schultz, P.Compitello, J.Grant, R. H.Kosmicki, J. A.Weisburd, B.Phu, W.Wilson, M. W.Laricchia, K. M.Goodrich, J. K.Goldstein, D.Goldstein, J. I.Vittal, C.Poterba, T.Baxter, S.Watts, N. A.Solomonson, M.gnomAD consortium,Tiao, G.Rehm, H. L.Neale, B. M.Talkowski, M. E.MacArthur, D. G.O'Donnell-Luria, A.Karczewski, K. J.Radivojac, P.Daly, M. J.Samocha, K. E.2024-04-13doi:10.1101/2024.04.11.588920Cold Spring Harbor Laboratory Press2024-04-13
<![CDATA[
A graph-based learning approach to predict the effects of gene perturbations on molecular phenotypes
]]>
https://biorxiv.org/cgi/content/short/2026.03.20.712202v1?rss=1"
Jin, Y.Sverchkov, Y.Sushkova, A.Ohtake, M.Emfinger, C.Craven, M.2026-03-23doi:10.64898/2026.03.20.712202Cold Spring Harbor Laboratory Press2026-03-23
<![CDATA[
SEEK-VEC: Robust Latent Structure Discovery via Ensemble Topic Modeling
]]>
https://biorxiv.org/cgi/content/short/2025.12.12.693799v1?rss=1"
Danning, R.Ke, Z. T.Ma, R.Lin, X.2025-12-14doi:10.64898/2025.12.12.693799Cold Spring Harbor Laboratory Press2025-12-14
<![CDATA[
Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq
]]>
https://biorxiv.org/cgi/content/short/2025.02.02.636107v1?rss=1"
Zhang, H.Li, X.Song, D.Yukselen, O.Nanda, S.Kucukural, A.Li, J. J.Garber, M.Walhout, A. J. M.2025-02-03doi:10.1101/2025.02.02.636107Cold Spring Harbor Laboratory Press2025-02-03
<![CDATA[
SPLENDID incorporates continuous genetic ancestry in biobank-scale data to improve polygenic risk prediction across diverse populations
]]>
https://biorxiv.org/cgi/content/short/2024.10.14.618256v1?rss=1"
Chen, T.Zhang, H.Mazumder, R.Lin, X.2024-10-17doi:10.1101/2024.10.14.618256Cold Spring Harbor Laboratory Press2024-10-17
<![CDATA[
cellSTAAR: Incorporating single-cell-sequencing-based functional data to boost power in rare variant association testing of non-coding regions
]]>
https://biorxiv.org/cgi/content/short/2025.04.23.650307v1?rss=1"
Van Buren, E.Zhang, Y.Li, X.Selvaraj, M. S.Li, Z.Zhou, H.Palmer, N. D.Arnett, D. K.Blangero, J.Boerwinkle, E.Cade, B. E.Carlson, J. C.Carson, A. P.Chen, Y.-D. I.Curran, J.Duggirala, R.Fornage, M.Franceschini, N.Graff, M.Gu, C.Guo, X.He, J.Heard-Cosa, N.Hou, L.Hung, Y.-J.Kalyani, R. R.Kardia, S. L. R.Kooperberg, C.Kral, B. G.Lange, L.Li, C.Liu, S.Lloyd-Jones, D.Loos, R. J. F.Manichaikul, A. W.Martin, L. W.Mathias, R.Minster, R.Mitchell, B. D.Mychaleckyj, J. C.Naseri, T.North, K.O'Connell, J.Perry, J. A.Peyse2025-04-26doi:10.1101/2025.04.23.650307Cold Spring Harbor Laboratory Press2025-04-26
<![CDATA[
Short-Context Regulatory DNA Language Models with Motif-Discovery Regularization
]]>
https://biorxiv.org/cgi/content/short/2026.02.05.703637v1?rss=1"
Patel, A.Kundaje, A.2026-02-06doi:10.64898/2026.02.05.703637Cold Spring Harbor Laboratory Press2026-02-06
<![CDATA[
High false sign rates in transcriptome-wide association studies
]]>
https://biorxiv.org/cgi/content/short/2025.12.19.695550v1?rss=1"
Gerlach, P. A.Milind, N.Spence, J. P.Pritchard, J. K.2025-12-20doi:10.64898/2025.12.19.695550Cold Spring Harbor Laboratory Press2025-12-20
<![CDATA[
Gradient-aware modeling advances AI-driven prediction of genetic perturbation effects
]]>
https://biorxiv.org/cgi/content/short/2025.10.03.680360v1?rss=1"
Jerby, L.Zhu, D.2025-10-05doi:10.1101/2025.10.03.680360Cold Spring Harbor Laboratory Press2025-10-05
<![CDATA[
Regulatory network topology and the genetic architecture of gene expression
]]>
https://biorxiv.org/cgi/content/short/2025.08.12.669924v1?rss=1"
Aguirre, M.Spence, J. P.Sella, G.Pritchard, J. K.2025-08-13doi:10.1101/2025.08.12.669924Cold Spring Harbor Laboratory Press2025-08-13
<![CDATA[
Robust self-supervised machine learning for single cell embeddings and annotations
]]>
https://biorxiv.org/cgi/content/short/2025.06.05.658097v1?rss=1"
Yeh, C. Y.Sun, M. W.Zhu, D.Jerby, L.2025-06-08doi:10.1101/2025.06.05.658097Cold Spring Harbor Laboratory Press2025-06-08
<![CDATA[
Focus on single gene effects limits discovery and interpretation of complex trait-associated variants
]]>
https://biorxiv.org/cgi/content/short/2025.06.06.658175v1?rss=1"
Lawrence, K. A.Gjorgjieva, T.Montgomery, S. B.2025-06-06doi:10.1101/2025.06.06.658175Cold Spring Harbor Laboratory Press2025-06-06
<![CDATA[
Redirecting cytotoxic lymphocytes to breast cancer tumors via metabolite-sensing receptors
]]>
https://biorxiv.org/cgi/content/short/2025.03.21.644686v1?rss=1"
Kim, Y. M.Akana, R.Sun, C.Laveroni, O.Jerby, L.2025-03-25doi:10.1101/2025.03.21.644686Cold Spring Harbor Laboratory Press2025-03-25
<![CDATA[
Mapping the regulatory effects of common and rare non-coding variants across cellular and developmental contexts in the brain and heart
]]>
https://biorxiv.org/cgi/content/short/2025.02.18.638922v1?rss=1"
Marderstein, A. R.Kundu, S.Padhi, E. M.Deshpande, S.Wang, A.Robb, E.Sun, Y.Yun, C. M.Pomales-Matos, D.Xie, Y.Nachun, D.Jessa, S.Kundaje, A.Montgomery, S. B.2025-02-19doi:10.1101/2025.02.18.638922Cold Spring Harbor Laboratory Press2025-02-19
<![CDATA[
Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq
]]>
https://biorxiv.org/cgi/content/short/2025.01.22.634424v1?rss=1"
Ota, M.Spence, J. P.Zeng, T.Dann, E.Marson, A.Pritchard, J. K.2025-01-24doi:10.1101/2025.01.22.634424Cold Spring Harbor Laboratory Press2025-01-24
<![CDATA[
ChromBPNet: bias factorized, base-resolution deep learning models of chromatin accessibility reveal cis-regulatory sequence syntax, transcription factor footprints and regulatory variants
]]>
https://biorxiv.org/cgi/content/short/2024.12.25.630221v1?rss=1"
Pampari, A.Shcherbina, A.Kvon, E.Kosicki, M.Nair, S.Kundu, S.Kathiria, A. S.Risca, V. I.Kuningas, K.Alasoo, K.Greenleaf, W.Pennacchio, L.Kundaje, A.2024-12-25doi:10.1101/2024.12.25.630221Cold Spring Harbor Laboratory Press2024-12-25
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Specificity, length, and luck: How genes are prioritized by rare and common variant association studies
]]>
https://biorxiv.org/cgi/content/short/2024.12.12.628073v1?rss=1"
Spence, J. P.Mostafavi, H.Ota, M.Milind, N.Gjorgjieva, T.Smith, C. J.Simons, Y. B.Sella, G.Pritchard, J. K.2024-12-16doi:10.1101/2024.12.12.628073Cold Spring Harbor Laboratory Press2024-12-16
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Directionality of Transcriptional Regulatory Elements
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https://biorxiv.org/cgi/content/short/2024.12.01.621925v1?rss=1"
Chen, Y.Shah, S. R.Leung, A.Paramo, M. I.Cochran, K.Kundaje, A.Clark, A. G.Lis, J. T.Yu, H.2024-12-02doi:10.1101/2024.12.01.621925Cold Spring Harbor Laboratory Press2024-12-02
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Dissecting the cis-regulatory syntax of transcription initiation with deep learning
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https://biorxiv.org/cgi/content/short/2024.05.28.596138v1?rss=1"
Cochran, K.Yin, M.Mantripragada, A.Schreiber, J.Marinov, G. K.Kundaje, A.2024-06-01doi:10.1101/2024.05.28.596138Cold Spring Harbor Laboratory Press2024-06-01
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Gene regulatory network structure informs the distribution of perturbation effects
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https://biorxiv.org/cgi/content/short/2024.07.04.602130v1?rss=1"
Aguirre, M.Spence, J. P.Sella, G.Pritchard, J. K.2024-07-05doi:10.1101/2024.07.04.602130Cold Spring Harbor Laboratory Press2024-07-05
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Mutagenesis Sensitivity Mapping of HumanEnhancers In Vivo
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https://biorxiv.org/cgi/content/short/2024.09.06.611737v1?rss=1"
Kosicki, M.Zhang, B.Pampari, A.Akiyama, J. A.Playzer-Frick, I.Novak, C. S.Tran, S.Zhu, Y.Kato, M.Hunter, R. D.von Maydell, K.Barton, S.Beckman, E.Kundaje, A.Dickel, D. E.Visel, A.Pennacchio, L. A.2024-09-08doi:10.1101/2024.09.06.611737Cold Spring Harbor Laboratory Press2024-09-08
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A model for accurate quantification of CRISPR effects in pooled FACS screens
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https://biorxiv.org/cgi/content/short/2024.06.17.599448v1?rss=1"
Pimentel, H.Freimer, J.Arce, M. M.Garrido, C. M.Marson, A.Pritchard, J. K.2024-06-18doi:10.1101/2024.06.17.599448Cold Spring Harbor Laboratory Press2024-06-18
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regionalpcs: improved discovery of DNA methylation associations with complex traits
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https://biorxiv.org/cgi/content/short/2024.05.01.590171v1?rss=1"
Eulalio, T.Sun, M. W.Gevaert, O.Greicius, M. D.Montine, T. J.Nachun, D.Montgomery, S. B.2024-05-01doi:10.1101/2024.05.01.590171Cold Spring Harbor Laboratory Press2024-05-01
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Characterizing spatial functional microniches with SpaceTravLR
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https://biorxiv.org/cgi/content/short/2025.11.13.688264v1?rss=1"
Ramjattun, K.Wang, A.Lee, H.Giri, S.Chen, Y.MacDonald, W. A.Lord, N.Poholek, A. C.Lee, Y.Das, J.2025-11-14doi:10.1101/2025.11.13.688264Cold Spring Harbor Laboratory Press2025-11-14
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A unified network systems approach uncovers a core novel program underlying T follicular helper cell differentiation
]]>
https://biorxiv.org/cgi/content/short/2025.08.19.670906v1?rss=1"
Omelchenko, A. A.Rahman, S. A.Viswanadham, V. V.Yuen, G. J.Del Rio Estrada, P. M.D'Onofrio, V.Chen, Y.Sun, N.Mattoo, H.Varma, C. G.Salgado, G.Nava, M. S.Ruiz, L. C.Rivera, D. D.Rios, S. A.Kasturi, S. P.Ribeiro, S. P.Shlomchik, M. J.Poholek, A. C.Pillai, S. S.Elsner, R. A.Mahajan, V. S.Das, J.2025-08-24doi:10.1101/2025.08.19.670906Cold Spring Harbor Laboratory Press2025-08-24
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Expanding the DNA Motif Lexicon of the Transcriptional Regulatory Code
]]>
https://biorxiv.org/cgi/content/short/2025.07.09.662874v1?rss=1"
Fan, J.Chaudhri, V. K.Bisht, D.Pease, N. A.Hall, D. R.Gerges, P.Yi, V. F.Kales, S.Ho, C.-H.Das, J.Ray, J. P.Tewhey, R.Meyer, C. A.Sahni, N.Singh, H.2025-07-15doi:10.1101/2025.07.09.662874Cold Spring Harbor Laboratory Press2025-07-15
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Sliding Window INteraction Grammar (SWING): a generalized interaction language model for peptide and protein interactions
]]>
https://biorxiv.org/cgi/content/short/2024.05.01.592062v1?rss=1"
Omelchenko, A. A.Siwek, J. C.Chhibbar, P.Arshad, S.Nazarali, I.Nazarali, K.Rosengart, A.Rahimikollu, J.Tilstra, J.Shlomchik, M. J.Koes, D. R.Joglekar, A. V.Das, J.2024-05-04doi:10.1101/2024.05.01.592062Cold Spring Harbor Laboratory Press2024-05-04