Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens
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Abstract
Most variants associated with complex traits and diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome with unknown effects. Using ancestrally diverse, biobank-scale GWAS data, massively parallel CRISPR screens, and single-cell transcriptomic and proteomic sequencing, we discovered 124 cis -target genes of 91 noncoding blood trait GWAS loci. Using precise variant insertion through base editing, we connected specific variants with gene expression changes. We also identified trans -effect networks of noncoding loci when cis target genes encoded transcription factors or microRNAs. Networks were themselves enriched for GWAS variants and demonstrated polygenic contributions to complex traits. This platform enables massively parallel characterization of the target genes and mechanisms of human noncoding variants in both cis and trans .
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PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437 · see citing works
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252 · see citing works
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247 · see citing works
Self-citationAn integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
Integrated analysis of multimodal single-cell data
Hao, Y., Hao, S., Andersen-Nissen, E., Mauck, W. M., Zheng, S., Butler, A., Lee, M. J., Wilk, A. J., Darby, C., Zagar, M., et al. (2020) · doi:10.1101/2020.10.12.335331 · Cited by 15,508 · see citing works
Self-citationComprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453 · see citing works
Self-citationGCTA: a tool for genome-wide complex trait analysis
Yang, J., Lee, S. H., Goddard, M. E., & Visscher, P. M. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.11.011 · Cited by 8,279 · see citing works
The Ensembl Variant Effect Predictor
McLaren, W., Gil, L., Hunt, S. E., Riat, H. S., Ritchie, G. R. S., Thormann, A., Flicek, P., & Cunningham, F. (2016) · Genome Biology · doi:10.1186/s13059-016-0974-4 · Cited by 8,099 · see citing works
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353 · see citing works
Predicting effective microRNA target sites in mammalian mRNAs
Agarwal, V., Bell, G. W., Nam, J.-W., & Bartel, D. P. (2015) · eLife · doi:10.7554/elife.05005 · Cited by 7,318 · see citing works
The GTEx Consortium atlas of genetic regulatory effects across human tissues
The GTEx Consortium, Aguet, F., Anand, S., Ardlie, K. G., Gabriel, S., Getz, G. A., Graubert, A., Hadley, K., Handsaker, R. E., Huang, K. H., et al. (2020) · Science · doi:10.1126/science.aaz1776 · Cited by 5,547 · see citing works
Self-citationProgrammable editing of a target base in genomic DNA without double-stranded DNA cleavage
Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A., & Liu, D. R. (2016) · Nature · doi:10.1038/nature17946 · Cited by 5,437 · see citing works
Improved vectors and genome-wide libraries for CRISPR screening
Sanjana, N. E., Shalem, O., & Zhang, F. (2014) · Nature Methods · doi:10.1038/nmeth.3047 · Cited by 5,239 · see citing works
Self-citationDNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741 · see citing works
Genetic effects on gene expression across human tissues
GTEx Consortium (2017) · Nature · doi:10.1038/nature24277 · Cited by 4,036 · see citing works
Buniello, A., MacArthur, J. A. L., Cerezo, M., Harris, L. W., Hayhurst, J., Malangone, C., McMahon, A., Morales, J., Mountjoy, E., Sollis, E., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1120 · Cited by 4,000 · see citing works
Simultaneous epitope and transcriptome measurement in single cells
Stoeckius, M., Hafemeister, C., Stephenson, W., Houck-Loomis, B., Chattopadhyay, P. K., Swerdlow, H., Satija, R., & Smibert, P. (2017) · Nature Methods · doi:10.1038/nmeth.4380 · Cited by 3,098 · see citing works
Self-citationClinical use of current polygenic risk scores may exacerbate health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2019) · Nature Genetics · doi:10.1038/s41588-019-0379-x · Cited by 2,831 · see citing works
Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation
Gilbert, L. A., Horlbeck, M. A., Adamson, B., Villalta, J. E., Chen, Y., Whitehead, E. H., Guimaraes, C., Panning, B., Ploegh, H. L., Bassik, M. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.029 · Cited by 2,728 · see citing works
Hematopoiesis: An Evolving Paradigm for Stem Cell Biology
Orkin, S. H., & Zon, L. I. (2008) · Cell · doi:10.1016/j.cell.2008.01.025 · Cited by 2,570 · see citing works
HiC-Pro: an optimized and flexible pipeline for Hi-C data processing.
Servant, N., Varoquaux, N., Lajoie, B. R., Viara, E., Chen, C.-J., Vert, J.-P., Heard, E., Dekker, J., & Barillot, E. (2015) · Genome Biology · doi:10.1186/s13059-015-0831-x · Cited by 2,565 · see citing works
An atlas of active enhancers across human cell types and tissues
The FANTOM Consortium, Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., et al. (2014) · Nature · doi:10.1038/nature12787 · Cited by 2,550 · see citing works
New insights into the genetic etiology of Alzheimer’s disease and related dementias
Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01024-z · Cited by 2,498 · cited 1× · see citing works
“This finding is further supported by prior work in the context of Alzheimer ’ s disease showing thatthe risk allele decreases miR-142 host gene promoter activity ( 62 , 63 ).”
ResultSelf-citationRegev, A., Teichmann, S. A., Lander, E. S., Amit, I., Benoist, C., Birney, E., Bodenmiller, B., Campbell, P., Carninci, P., Clatworthy, M., et al. (2017) · eLife · doi:10.7554/elife.27041 · Cited by 2,232 · see citing works
Meyers, R. M., Bryan, J. G., McFarland, J. M., Weir, B. A., Sizemore, A. E., Xu, H., Dharia, N. V., Montgomery, P. G., Cowley, G. S., Pantel, S., et al. (2017) · Nature Genetics · doi:10.1038/ng.3984 · Cited by 1,952 · see citing works
Dynamic Imaging of Genomic Loci in Living Human Cells by an Optimized CRISPR/Cas System
Chen, B., Gilbert, L. A., Cimini, B. A., Schnitzbauer, J., Zhang, W., Li, G., Park, J. S., Blackburn, E. H., Weissman, J. S., Qi, L. S., et al. (2013) · Cell · doi:10.1016/j.cell.2013.12.001 · Cited by 1,931 · see citing works
Transcriptome and genome sequencing uncovers functional variation in humans
The Geuvadis Consortium, Lappalainen, T., Sammeth, M., Friedländer, M. R., ‘t Hoen, P. A. C., Monlong, J., Rivas, M. A., Gonzàlez-Porta, M., Kurbatova, N., Griebel, T., et al. (2013) · Nature · doi:10.1038/nature12531 · Cited by 1,888 · see citing works
Self-citationDixit, A., Parnas, O., Li, B., Chen, J., Fulco, C. P., Jerby-Arnon, L., Marjanovic, N. D., Dionne, D., Burks, T., Raychowdhury, R., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.038 · Cited by 1,863 · see citing works
Recovering Gene Interactions from Single-Cell Data Using Data Diffusion
van Dijk, D., Sharma, R., Nainys, J., Yim, K., Kathail, P., Carr, A. J., Burdziak, C., Moon, K. R., Chaffer, C. L., Pattabiraman, D., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.061 · Cited by 1,829 · see citing works
Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Yang, J., DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Ferreira, T., Morris, A. P., Medland, S. E., Madden, P. A. F., Heath, A. C., Martin, N. G., Montgomery, G. W., et al. (2012) · Nature Genetics · doi:10.1038/ng.2213 · Cited by 1,712 · see citing works
The biochemical basis of microRNA targeting efficacy
(2019) · doi:10.1126/science.aav1741 · Cited by 1,570 · see citing works
Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
Walton, R. T., Christie, K. A., Whittaker, M. N., & Kleinstiver, B. P. (2020) · Science · doi:10.1126/science.aba8853 · Cited by 1,233 · see citing works
The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease
Astle, W. J., Elding, H., Jiang, T., Allen, D., Ruklisa, D., Mann, A. L., Mead, D., Bouman, H., Riveros-Mckay, F., Kostadima, M. A., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.042 · Cited by 1,224 · see citing works
Robust rank aggregation for gene list integration and meta-analysis
Kolde, R., Laur, S., Adler, P., & Vilo, J. (2012) · Bioinformatics · doi:10.1093/bioinformatics/btr709 · Cited by 1,195 · see citing works
Adamson, B., Norman, T. M., Jost, M., Cho, M. Y., Nuñez, J. K., Chen, Y., Villalta, J. E., Gilbert, L. A., Horlbeck, M. A., Hein, M. Y., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.048 · Cited by 1,193 · see citing works
Javierre, B. M., Burren, O. S., Wilder, S. P., Kreuzhuber, R., Hill, S. M., Sewitz, S., Cairns, J., Wingett, S. W., Várnai, C., Thiecke, M. J., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.037 · Cited by 1,046 · see citing works
Lun, A. T. L., Riesenfeld, S. J., Andrews, T. S., Dao, T. P., Gomes, T., Jamboree, P. I. T. 1. H. C. A., & Marioni, J. C. (2019) · Genome biology · doi:10.1186/s13059-019-1662-y · Cited by 1,042 · see citing works
BEDOPS: high-performance genomic feature operations
Neph, S. J., Kuehn, M. S., Reynolds, A. P., Haugen, E., Thurman, R. E., Johnson, A., Rynes, E., Maurano, M. T., Vierstra, J. D., Thomas, S., et al. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts277 · Cited by 971 · see citing works
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
Canver, M. C., Smith, E. C., Sher, F., Pinello, L., Sanjana, N. E., Shalem, O., Chen, D. D., Schupp, P. G., Vinjamur, D. S., Garcia, S. P., et al. (2015) · Nature · doi:10.1038/nature15521 · Cited by 886 · see citing works
Self-citationImpact of Genetic Polymorphisms on Human Immune Cell Gene Expression
Schmiedel, B. J., Singh, D., Madrigal, A., Valdovino-Gonzalez, A. G., White, B. M., Zapardiel-Gonzalo, J., Ha, B., Altay, G., Greenbaum, J. A., McVicker, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.022 · Cited by 867 · see citing works
FINEMAP: efficient variable selection using summary data from genome-wide association studies
Benner, C., Spencer, C. C. A., Havulinna, A. S., Salomaa, V., Ripatti, S., & Pirinen, M. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw018 · Cited by 815 · see citing works
An atlas of genetic influences on osteoporosis in humans and mice
23andMe Research Team, Morris, J. A., Kemp, J. P., Youlten, S. E., Laurent, L., Logan, J. G., Chai, R. C., Vulpescu, N. A., Forgetta, V., Kleinman, A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0302-x · Cited by 773 · see citing works
Self-citationMapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq
Replogle, J. M., Saunders, R. A., Pogson, A. N., Hussmann, J. A., Lenail, A., Guna, A., Mascibroda, L., Wagner, E. J., Adelman, K., Lithwick-Yanai, G., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.013 · Cited by 751 · cited 2× · see citing works
“To help distinguish direct and indirect regulation, we used a prior genome-wide Perturb-seq (GWPS) study in the same cell line (K562) to determine whether APOE or APOC1 regulate one another ( 47 ).”
MethodGenetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells
Chen, L., Ge, B., Casale, F. P., Vasquez, L., Kwan, T., Garrido-Martín, D., Watt, S., Yan, Y., Kundu, K., Ecker, S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.026 · Cited by 679 · see citing works
Self-citationThe Polygenic and Monogenic Basis of Blood Traits and Diseases
Vuckovic, D., Bao, E. L., Akbari, P., Lareau, C. A., Mousas, A., Jiang, T., Chen, M.-H., Raffield, L. M., Tardaguila, M., Huffman, J. E., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.008 · Cited by 671 · see citing works
Genome-wide enhancer maps link risk variants to disease genes
Nasser, J., Bergman, D. T., Fulco, C. P., Guckelberger, P., Doughty, B. R., Patwardhan, T. A., Jones, T. R., Nguyen, T. H., Ulirsch, J. C., Lekschas, F., et al. (2021) · Nature · doi:10.1038/s41586-021-03446-x · Cited by 669 · see citing works
Chen, M.-H., Raffield, L. M., Mousas, A., Sakaue, S., Huffman, J. E., Moscati, A., Trivedi, B., Jiang, T., Akbari, P., Vuckovic, D., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.045 · Cited by 661 · see citing works
Systematic mapping of functional enhancer–promoter connections with CRISPR interference
Fulco, C. P., Munschauer, M., Anyoha, R., Munson, G., Grossman, S. R., Perez, E. M., Kane, M., Cleary, B., Lander, E. S., & Engreitz, J. M. (2016) · Science · doi:10.1126/science.aag2445 · Cited by 643 · see citing works
A Genome-wide Framework for Mapping Gene Regulation via Cellular Genetic Screens
Gasperini, M., Hill, A. J., McFaline-Figueroa, J. L., Martin, B., Kim, S., Zhang, M. D., Jackson, D., Leith, A., Schreiber, J., Noble, W. S., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.029 · Cited by 613 · see citing works
Common genetic variation drives molecular heterogeneity in human iPSCs
Kilpinen, H., Goncalves, A., Leha, A., Afzal, V., Alasoo, K., Ashford, S., Bala, S., Bensaddek, D., Casale, F. P., Culley, O. J., et al. (2017) · Nature · doi:10.1038/nature22403 · Cited by 586 · see citing works
Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells
Daniloski, Z., Jordan, T. X., Wessels, H., Hoagland, D. A., Kasela, S., Legut, M., Maniatis, S., Mimitou, E. P., Lu, L., Geller, E. T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.030 · Cited by 549 · see citing works
Self-citationMimitou, E. P., Cheng, A., Montalbano, A., Hao, S., Stoeckius, M., Legut, M., Roush, T., Herrera, A., Papalexi, E., Ouyang, Z., et al. (2019) · Nature Methods · doi:10.1038/s41592-019-0392-0 · Cited by 520 · see citing works
Self-citationGenetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens
Nédélec, Y., Sanz, J., Baharian, G., Szpiech, Z. A., Pacis, A., Dumaine, A., Grenier, J.-C., Freiman, A., Sams, A. J., Hebert, S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.025 · Cited by 512 · see citing works
Bayesian refinement of association signals for 14 loci in 3 common diseases
Maller, J., McVean, G., Byrnes, J., Vukcevic, D., Palin, K., Su, Z., Howson, J. M. M., Auton, A., Myers, S. R., Morris, A. P., et al. (2012) · Nature Genetics · doi:10.1038/ng.2435 · Cited by 481 · see citing works
Genetic adaptation and Neandertal admixture shaped the immune system of human populations
Quach, H., Rotival, M., Pothlichet, J., Loh, Y.-H. E., Dannemann, M., Zidane, N., Laval, G., Patin, E., Harmant, C., Lopez, M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.024 · Cited by 475 · see citing works
An enhanced CRISPR repressor for targeted mammalian gene regulation
Yeo, N. C., Chavez, A., Lance‐Byrne, A., Chan, Y., Menn, D. J., Milanova, D., Kuo, C., Guo, X., Sharma, S., Tung, A., et al. (2018) · Nature Methods · doi:10.1038/s41592-018-0048-5 · Cited by 472 · see citing works
Klann, T. S., Black, J. B., Chellappan, M., Safi, A., Song, L., Hilton, I. B., Crawford, G. E., Reddy, T. E., & Gersbach, C. A. (2017) · Nature Biotechnology · doi:10.1038/nbt.3853 · Cited by 447 · see citing works
Passive and active DNA methylation and the interplay with genetic variation in gene regulation
Gutierrez-Arcelus, M., Lappalainen, T., Montgomery, S. B., Buil, A., Ongen, H., Yurovsky, A., Bryois, J., Giger, T., Romano, L., Planchon, A., et al. (2013) · eLife · doi:10.7554/elife.00523 · Cited by 440 · see citing works
Self-citationA compendium of uniformly processed human gene expression and splicing quantitative trait loci
Kerimov, N., Hayhurst, J. D., Peikova, K., Manning, J. R., Walter, P., Kolberg, L., Samoviča, M., Sakthivel, M. P., Kuzmin, I., Trevanion, S. J., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00924-w · Cited by 440 · see citing works
Massively parallel Cas13 screens reveal principles for guide RNA design
Wessels, H.-H., Méndez-Mancilla, A., Guo, X., Legut, M., Daniloski, Z., & Sanjana, N. E. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0456-9 · Cited by 418 · see citing works
Self-citationGlobal Biobank Meta-analysis Initiative: Powering genetic discovery across human disease
Zhou, W., Kanai, M., Wu, K.-H., Rasheed, H., Tsuo, K., Hirbo, J. B., Wang, Y., Bhattacharya, A., Zhao, H., Namba, S., et al. (2022) · Cell Genomics · doi:10.1016/j.xgen.2022.100192 · Cited by 414 · see citing works
Dempster, J. M., Boyle, I., Vázquez, F., Root, D. E., Boehm, J. S., Hahn, W. C., Tsherniak, A., & McFarland, J. M. (2021) · Genome biology · doi:10.1186/s13059-021-02540-7 · Cited by 400 · see citing works
Dempster, J. M., Rossen, J., Kazachkova, M., Pan, J., Kugener, G., Root, D., & Tsherniak, A. (2019) · bioRxiv · doi:10.1101/720243 · Cited by 348 · see citing works
Optimized base editors enable efficient editing in cells, organoids and mice
Zafra, M. P., Schatoff, E. M., Katti, A., Foronda, M., Breinig, M., Schweitzer, A. Y., Simon, A., Han, T., Goswami, S., Montgomery, E., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4194 · Cited by 347 · see citing works
HIPSCI Consortium, Alasoo, K., Rodrigues, J., Mukhopadhyay, S., Knights, A. J., Mann, A. L., Kundu, K., Hale, C., Dougan, G., & Gaffney, D. J. (2018) · Nature Genetics · doi:10.1038/s41588-018-0046-7 · Cited by 338 · see citing works
Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits
Ulirsch, J. C., Nandakumar, S. K., Wang, L., Giani, F. C., Zhang, X., Rogov, P., Melnikov, A., McDonel, P., Do, R., Mikkelsen, T. S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.048 · Cited by 328 · see citing works
Detection and removal of barcode swapping in single-cell RNA-seq data
Griffiths, J. A., Richard, A. C., Bach, K., Lun, A. T. L., & Marioni, J. C. (2018) · Nature Communications · doi:10.1038/s41467-018-05083-x · Cited by 324 · see citing works
Massively parallel assessment of human variants with base editor screens
Hanna, R. E., Hegde, M., Fagre, C. R., DeWeirdt, P. C., Sangree, A. K., Szegletes, Z., Griffith, A., Feeley, M. N., Sanson, K. R., Baidi, Y., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.012 · Cited by 316 · see citing works
Massively parallel assessment of human variants with base editor screens
Hanna, R. E., Hegde, M., Fagre, C. R., DeWeirdt, P. C., Sangree, A. K., Szegletes, Z., Griffith, A., Feeley, M. N., Sanson, K. R., Baidi, Y., et al. (2020) · doi:10.1101/2020.05.17.100818 · Cited by 314 · cited 1× · see citing works
“We observed up to ~70% knockdown of CD46 when targeting splice sites with diverse PAM sequences and an average knockdown of 27% ( n = 12 target sites), similar to prior pooled screens using base editing ( 52 , 53 ), (fig.”
Integrated cross-study datasets of genetic dependencies in cancer
Pacini, C., Dempster, J. M., Boyle, I. A., Gonçalves, E., Najgebauer, H., Karakoç, E., van der Meer, D., Barthorpe, A. S., Lightfoot, H., Jaaks, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-021-21898-7 · Cited by 294 · see citing works
Mägi, R., Horikoshi, M., Sofer, T., Mahajan, A., Kitajima, H., Franceschini, N., McCarthy, M. I., & Morris, A. P. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx280 · Cited by 283 · see citing works
Mancuso, N., Shi, H., Goddard, P. C., Kichaev, G., Gusev, A., & Paşaniuc, B. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.01.031 · Cited by 265 · see citing works
Benner, C., Havulinna, A. S., Järvelin, M., Salomaa, V. V., Ripatti, S., & Pirinen, M. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.08.012 · Cited by 244 · see citing works
Identification of significant chromatin contacts from HiChIP data by FitHiChIP
Bhattacharyya, S., Chandra, V., Vijayanand, P., & Ay, F. (2019) · Nature Communications · doi:10.1038/s41467-019-11950-y · Cited by 238 · see citing works
Functional interrogation of DNA damage response variants with base editing screens
Cuella-Martin, R., Hayward, S. B., Fan, X., Chen, X., Huang, J., Taglialatela, A., Leuzzi, G., Zhao, J., Rabadán, R., Lü, C., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.041 · Cited by 233 · see citing works
Maurano, M. T., Haugen, E., Sandstrom, R. S., Vierstra, J. D., Shafer, A., Kaul, R., & Stamatoyannopoulos, J. A. (2015) · Nature Genetics · doi:10.1038/ng.3432 · Cited by 211 · see citing works
Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twins
Buil, A., Brown, A. A., Lappalainen, T., Viñuela, A., Davies, M. N., Zheng, H.-F., Richards, J. B., Glass, D., Small, K. S., Durbin, R. M., et al. (2014) · Nature Genetics · doi:10.1038/ng.3162 · Cited by 210 · see citing works
Self-citationInterrogation of human hematopoiesis at single-cell and single-variant resolution
Ulirsch, J. C., Lareau, C. A., Bao, E. L., Ludwig, L. S., Guo, M. H., Benner, C., Satpathy, A. T., Kartha, V. K., Salem, R. M., Hirschhorn, J. N., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0362-6 · Cited by 208 · see citing works
Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond
Fuior, E. V., & Gafencu, A. V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235939 · Cited by 190 · see citing works
Landscape of allele-specific transcription factor binding in the human genome
Abramov, S., Boytsov, A., Bykova, D., Penzar, D., Yevshin, I., Kolmykov, S. K., Fridman, M. V., Favorov, A. V., Vorontsov, I. E., Baulin, E. F., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23007-0 · Cited by 179 · see citing works
A genome-scale screen for synthetic drivers of T cell proliferation
Legut, M., Gajic, Z. Z., Guarino, M., Daniloski, Z., Rahman, J. A., Xue, X., Lu, C., Lu, L., Mimitou, E. P., Hao, S., et al. (2022) · Nature · doi:10.1038/s41586-022-04494-7 · Cited by 177 · see citing works
Self-citationFrom variant to function in human disease genetics
Lappalainen, T., & MacArthur, D. G. (2021) · Science · doi:10.1126/science.abi8207 · Cited by 175 · see citing works
Self-citationPanopoulos, A. D., D’Antonio, M., Benaglio, P., Williams, R. M., Hashem, S. I., Schuldt, B. M., DeBoever, C., Arias, A. D., Garcia, M., Nelson, B., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.03.012 · Cited by 162 · see citing works
Pashos, E. E., Park, Y., Wang, X., Raghavan, A., Yang, W., Abbey, D., Peters, D., Arbelaez, J., Hernandez, M., Kuperwasser, N., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.03.017 · Cited by 160 · see citing works
APOE and cholesterol homeostasis in Alzheimer's disease
Leduc, V., Jasmin, S. B., & Poirier, J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.07.008 · Cited by 158 · see citing works
FlashFry: A fast and flexible tool for large-scale CRISPR target design
McKenna, A., & Shendure, J. (2018) · BMC Biology · doi:10.1186/s12915-018-0545-0 · Cited by 152 · see citing works
Gasperini, M., Findlay, G. M., McKenna, A., Milbank, J. H., Lee, C., Zhang, M. D., Cusanovich, D. A., & Shendure, J. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.06.010 · Cited by 143 · see citing works
Multiple genes encode the human Na+,K+-ATPase catalytic subunit.
Shull, M. M., & Lingrel, J. B. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.12.4039 · Cited by 137 · see citing works
Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis
Osawa, M. (2002) · Blood · doi:10.1182/blood-2002-01-0182 · Cited by 130 · see citing works
Kluesner, M. G., Lahr, W. S., Lonetree, C.-L., Smeester, B. A., Qiu, X., Slipek, N. J., Claudio Vázquez, P. N., Pitzen, S. P., Pomeroy, E. J., Vignes, M. J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22009-2 · Cited by 121 · see citing works
Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and numberPreprint
Sankaran, V. G., Ludwig, L. S., Sicińska, E., Xu, J., Bauer, D. E., Eng, J. C., Patterson, H. C., Metcalf, R. A., Natkunam, Y., Orkin, S. H., et al. (2012) · Genes & Development · doi:10.1101/gad.197020.112 · Cited by 119 · see citing works
A role for RUNX1 in hematopoiesis and myeloid leukemia
Ichikawa, M., Yoshimi, A., Nakagawa, M. M., Nishimoto, N., Watanabe‐Okochi, N., & Kurokawa, M. (2013) · International Journal of Hematology · doi:10.1007/s12185-013-1347-3 · Cited by 118 · see citing works
From cytopenia to leukemia: the role of Gfi1 and Gfi1b in blood formation
Möröy, T., Vaßen, L., Wilkes, B. C., & Khandanpour, C. (2015) · Blood · doi:10.1182/blood-2015-06-655043 · Cited by 110 · see citing works
Liscovitch-Brauer, N., Montalbano, A., Deng, J., Méndez-Mancilla, A., Wessels, H.-H., Moss, N. G., Kung, C.-Y., Sookdeo, A., Guo, X., Geller, E., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00902-x · Cited by 107 · see citing works
Self-citationGarnache‐Ottou, F. (2004) · Blood · doi:10.1182/blood-2004-06-2416 · Cited by 101 · see citing works
Propris, M. S. D., Raponi, S., Diverio, D., et al. (2011) · Haematologica · doi:10.3324/haematol.2011.043786 · Cited by 100 · see citing works
PICKLES: the database of pooled in-vitro CRISPR knockout library essentiality screens
Lenoir, W. F., Lim, T. L., & Hart, T. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx993 · Cited by 94 · see citing works
SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis
Barry, T., Wang, X., Morris, J. A., Roeder, K., & Katsevich, E. (2021) · Genome Biology · doi:10.1186/s13059-021-02545-2 · Cited by 86 · see citing works
Self-citationChen, C., Chen, T., Feng, Y. A., Yu, M., Lin, S., Longchamps, R. J., Wang, S., Hsu, Y., Yang, H., Kuo, P., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100436 · Cited by 82 · see citing works
Fauman, E. B., & Hyde, C. L. (2022) · BMC Bioinformatics · doi:10.1186/s12859-022-04706-x · Cited by 81 · see citing works
miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis
Chapnik, E., Rivkin, N., Mildner, A., Beck, G., Pasvolsky, R., Metzl-Raz, E., Birger, Y., Amir, G., Tirosh, I., Porat, Z., et al. (2014) · eLife · doi:10.7554/elife.01964 · Cited by 79 · see citing works
BGEN: a binary file format for imputed genotype and haplotype dataPreprint
Band, G., & Marchini, J. (2018) · bioRxiv · doi:10.1101/308296 · Cited by 78 · see citing works
Genome-Wide Association Study of Lp-PLA2 Activity and Mass in the Framingham Heart Study
Suchindran, S., Rivedal, D. D., Guyton, J. R., Milledge, T., Gao, X., Benjamin, A. M., Rowell, J. V., Ginsburg, G. S., & McCarthy, J. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000928 · Cited by 75 · see citing works
Legut, M., Daniloski, Z., Xue, X., McKenzie, D., Guo, X., Wessels, H., & Sanjana, N. E. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.02.010 · Cited by 71 · see citing works
Self-citationGasiorek, J. J., & Blank, V. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1866-6 · Cited by 64 · see citing works
Chen, C.-Y., Chen, T.-T., Feng, Y.-C. A., Yu, M.-R., Lin, S.-C., Longchamps, R. J., Wang, S.-H., Hsu, Y.-H., Yang, H. I., Kuo, P.-H., et al. (2021) · medRxiv · doi:10.1101/2021.04.12.21255236 · Cited by 63 · see citing works
The Role of Neutrophils in Hypertension
Araos, P. A., Figueroa, S. M., & Amador, C. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228536 · Cited by 57 · see citing works
Ulirsch, J., Lacy, J., An, X., Mohandas, N., Mikkelsen, T., & Sankaran, V. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004890 · Cited by 51 · see citing works
Association of ATP1A1 and Dear Single-Nucleotide Polymorphism Haplotypes With Essential Hypertension
Glorioso, N., Herrera, V. L. M., Bagamasbad, P., Filigheddu, F., Troffa, C., Argiolas, G., Bulla, E., Decano, J. L., & Ruiz‐Opazo, N. (2007) · Circulation Research · doi:10.1161/01.res.0000267716.96196.60 · Cited by 49 · see citing works
C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis
Lepik, K., Annilo, T., Kukuškina, V., eQTLGen Consortium, Kisand, K., Kutalik, Z., Peterson, P., & Peterson, H. (2017) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1005766 · Cited by 48 · see citing works
Global Analysis of Enhancer Targets Reveals Convergent Enhancer-Driven Regulatory Modules
Xie, S., Armendariz, D. A., Zhou, P., Duan, J., & Hon, G. C. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.073 · Cited by 46 · see citing works
Chronos: a CRISPR cell population dynamics modelPreprint
Dempster, J. M., Boyle, I., Vázquez, F., Root, D. E., Boehm, J. S., Hahn, W. C., Tsherniak, A., & McFarland, J. M. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.25.432728 · Cited by 44 · see citing works
Transcription Factor GFI1B in Health and Disease
Anguita, E., Candel, F. J., Chaparro, A., & Roldán‐Etcheverry, J. J. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00054 · Cited by 43 · see citing works
CRISPR Screens to Discover Functional Noncoding Elements
Wright, J. B., & Sanjana, N. E. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.06.004 · Cited by 41 · see citing works
Self-citationGfi1b regulates the level of Wnt/β-catenin signaling in hematopoietic stem cells and megakaryocytes
Shooshtarizadeh, P., Helness, A., Vadnais, C., Brouwer, N. P. M., Beauchemin, H., Chen, R., Bagci, H., Staal, F. J. T., Côté, J., & Möröy, T. (2019) · Nature Communications · doi:10.1038/s41467-019-09273-z · Cited by 41 · see citing works
miR-144/451 in hematopoiesis and beyond
Wang, T., Wu, F., & Yu, D. (2019) · ExRNA · doi:10.1186/s41544-019-0035-8 · Cited by 40 · see citing works
Wünnemann, F., Tadjo, T. F., Beaudoin, M., Lalonde, S., Lo, K. S., Kleinstiver, B. P., & Lettre, G. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010680 · Cited by 39 · see citing works
Gryder, B. E., Khan, J., & Stanton, B. Z. (2020) · Nature Protocols · doi:10.1038/s41596-019-0285-9 · Cited by 35 · see citing works
Beauchemin, H., & Möröy, T. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.591099 · Cited by 32 · see citing works
Ghanbari, M., Munshi, S. T., Ma, B., Lendemeijer, B., Bansal, S., Adams, H. H. H., Wang, W., Goth, K., Slump, D. E., van den Hout, M. C. G. N., et al. (2019) · Human Mutation · doi:10.1002/humu.23872 · Cited by 31 · see citing works
Blatt, K., Herrmann, H., Hoermann, G., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2811 · Cited by 28 · see citing works
Ikaros: master of hematopoiesis, agent of leukemia
Davis, K. L. (2011) · Therapeutic Advances in Hematology · doi:10.1177/2040620711412419 · Cited by 26 · see citing works
Self-citationGenetic variants modulate gene expression statin response in human lymphoblastoid cell lines
Theusch, E., Chen, Y. I., Rotter, J. I., Krauss, R. M., & Medina, M. W. (2020) · BMC Genomics · doi:10.1186/s12864-020-06966-4 · Cited by 23 · see citing works
Increasing the Targeting Scope of CRISPR Base Editing System Beyond NGG
Yu, S.-Y., Birkenshaw, A., Thomson, T., Carlaw, T., Zhang, L., & Ross, C. J. (2022) · The CRISPR Journal · doi:10.1089/crispr.2021.0109 · Cited by 23 · see citing works
Rowland, B., Venkatesh, S., Tardáguila, M., Wen, J., Rosen, J. D., Tapia, A. L., Sun, Q., Graff, M., Vuckovic, D., Lettre, G., et al. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac011 · Cited by 18 · see citing works
Li, B., Veturi, Y., Verma, A., Bradford, Y., Daar, E. S., Gulick, R. M., Riddler, S. A., Robbins, G. K., Lennox, J. L., Haas, D. W., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009464 · Cited by 14 · see citing works
From GWAS variant to function: A study of ∼148,000 variants for blood cell traits
Sun, Q., Crowley, C., Huang, L., Wen, J., Chen, J. C., Bao, E. L., Auer, P. L., Lettre, G., Reiner, A. P., Sankaran, V. G., et al. (2021) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2021.100063 · Cited by 14 · see citing works
Mapping the convergence of genes for coronary artery disease onto endothelial cell programsPreprint
Schnitzler, G. R., Kang, H. Y., Lee-Kim, V. S., Ma, X. R., Zeng, T., Angom, R. S., Fang, S., Vellarikkal, S. K., Zhou, R., Guo, K., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.01.514606 · Cited by 9 · see citing works
Multi-center integrated analysis of non-coding CRISPR screensPreprint
Yao, D., Tycko, J., Oh, J. W., Bounds, L. R., Gosai, S. J., Lataniotis, L., Mackay-Smith, A., Doughty, B. R., Gabdank, I., Schmidt, H., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.21.520137 · Cited by 9 · see citing works
The Role of Hex in Hemangioblast and Hematopoietic Development
Chan, R. J., Hromas, R., & Yöder, M. C. (2006) · Humana Press eBooks · doi:10.1385/1-59745-036-7:123 · Cited by 5 · see citing works
Wen, J., Lagler, T. M., Sun, Q., Yang, Y.-C., Chen, J.-W., Harigaya, Y., Sankaran, V., Hu, M., Reiner, A., Raffield, L., et al. (2021) · bioRxiv · doi:10.1371/journal.pgen.1009984 · Cited by 5 · see citing works
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Systematic differences in discovery of genetic effects on gene expression and complex traits
Mostafavi, H., Spence, J. P., Naqvi, S., & Pritchard, J. K. (2023) · Nature Genetics · doi:10.1038/s41588-023-01529-1 · Cited by 336 · see citing works
Scalable genetic screening for regulatory circuits using compressed Perturb-seq
Yao, D., Binan, L., Bezney, J., Simonton, B., Freedman, J., Frangieh, C. J., Dey, K., Geiger-Schuller, K., Eraslan, B., Gusev, A., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-01964-9 · Cited by 101 · see citing works
SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis
Barry, T., Wang, X., Morris, J. A., Roeder, K., & Katsevich, E. (2021) · Genome Biology · doi:10.1186/s13059-021-02545-2 · Cited by 86 · see citing works
Self-citationEfficient combinatorial targeting of RNA transcripts in single cells with Cas13 RNA Perturb-seq
Wessels, H.-H., Méndez-Mancilla, A., Hao, Y., Papalexi, E., Mauck, W. M., Lu, L., Morris, J. A., Mimitou, E. P., Smibert, P., Sanjana, N. E., et al. (2023) · Nature Methods · doi:10.1038/s41592-022-01705-x · Cited by 79 · see citing works
Self-citationBarry, T., Mason, K., Roeder, K., & Katsevich, E. (2024) · Genome Biology · doi:10.1186/s13059-024-03254-2 · Cited by 28 · see citing works
Self-citation
- Authors
- Morris, J. A., Caragine, C., Daniloski, Z., Domingo, J., Barry, T., Lu, L., Davis, K., Ziosi, M., Glinos, D. A., Hao, S., Mimitou, E. P., Smibert, P., Roeder, K., Katsevich, E., Lappalainen, T., & Sanjana, N. E.
- Affiliations
- New York Genome Center (US)
- Carnegie Mellon University (US)
- University of Pennsylvania (US)
- Science for Life Laboratory (SE)
- Corresponding author
- Lappalainen, Tuuli
- Sanjana, Neville E.
- ORCID
- Venue
- Science
- Published
- 2023-05-19
- Volume
- 380
- Issue
- 6646
- Pages
- eadh7699-eadh7699
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC10518238
- OpenAlex
- W4368347467
- Cited by
- 208
- References
- 133
- Citations by year
- 2026: 54 · 2025: 61 · 2024: 66 · 2023: 20 · 2022: 3 · 2021: 3 · 2020: 1
- FWCI
- 34.53
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (2113072)
- Cancer Research Institute
- American Heart Association (20POST35220040)
- Sidney Kimmel Foundation
- New York Genome Center (DP2HG010099)
- York University
- National Institutes of Health
- Defense Advanced Research Projects Agency (D18AP00053)
- Canadian Institutes of Health Research
- National Institute of Mental Health (R01MH106842, R01MH123184)
- National Human Genome Research Institute (UM1HG008901, K99HG012792, DP2HG010099)
- National Cancer Institute (D18AP00053, R01CA279135, R01CA218668)
- National Institute of General Medical Sciences (R01GM122924, R01GM138635)
- National Institute of Allergy and Infectious Diseases (R01AI176601)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- non-coding variants, GWAS loci, blood characteristics, single-cell CRISPR screens, base editing, transcription factors, microRNA, polygenic traits, gene expression regulation, biobank-scale data
- MeSH terms
- RNA-Seq, Blood Cells, Disease, Humans, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Proteomics, Genome-Wide Association Study, Single-Cell Analysis, Clustered Regularly Interspaced Short Palindromic Repeats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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