Dixit, A. et al. Perturb-Seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. Cell 167, 1853–1866.e17 (2016).
Replogle, J. M. et al. Mapping information-rich genotype–phenotype landscapes with genome-scale Perturb-seq. Cell 185, 2559–2575.e28 (2022).
Frangieh, C. J. et al. Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion. Nat. Genet. 53, 332–341 (2021).
Mimitou, E. P. et al. Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat. Methods 16, 409–412 (2019).
Rubin, A. J. et al. Coupled single-cell CRISPR screening and epigenomic profiling reveals causal gene regulatory networks. Cell 176, 361–376.e17 (2019).
Liscovitch-Brauer, N. et al. Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens. Nat. Biotechnol. 39, 1270–1277 (2021).
Pierce, S. E., Granja, J. M. & Greenleaf, W. J. High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer. Nat. Commun. 12, 2969 (2021).
Cheng, Y. et al. Perturb-tracing enables high-content screening of multiscale, global 3D genome regulators. Biophys. J. 123, 83a (2024).
Morris, J. A., Sun, J. S. & Sanjana, N. E. Next-generation forward genetic screens: uniting high-throughput perturbations with single-cell analysis. Trends Genet. 40, 118–133 (2023).
Huang, M. E. et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72, 567–572 (1988).
Datlinger, P. et al. Ultra-high-throughput single-cell RNA sequencing and perturbation screening with combinatorial fluidic indexing. Nat. Methods 18, 635–642 (2021).
Lareau, C. A. et al. Droplet-based combinatorial indexing for massive-scale single-cell chromatin accessibility. Nat. Biotechnol. 37, 916–924 (2019).
Zhang, H. et al. txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility. Genome Biol. 25, 78 (2024).
Morris, J. A. et al. Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens. Science 380, eadh7699 (2023).
Ma, S. et al. Chromatin potential identified by shared single-cell profiling of RNA and chromatin. Cell 183, 1103–1116.e20 (2020).
Cao, J. et al. Joint profiling of chromatin accessibility and gene expression in thousands of single cells. Science 361, 1380–1385 (2018).
Chen, S., Lake, B. B. & Zhang, K. High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell. Nat. Biotechnol. 37, 1452–1457 (2019).
Zhu, C. et al. An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome. Nat. Struct. Mol. Biol. 26, 1063–1070 (2019).
Datlinger, P. et al. Pooled CRISPR screening with single-cell transcriptome readout. Nat. Methods 14, 297–301 (2017).
Hill, A. J. et al. On the design of CRISPR-based single-cell molecular screens. Nat. Methods 15, 271–274 (2018).
Kadoch, C. & Crabtree, G. R. Mammalian SWI/SNF chromatin remodeling complexes and cancer: mechanistic insights gained from human genomics. Sci. Adv. 1, e1500447 (2015).
Jackson, E. M. et al. Genomic analysis using high-density single nucleotide polymorphism-based oligonucleotide arrays and multiplex ligation-dependent probe amplification provides a comprehensive analysis of INI1/SMARCB1 in malignant rhabdoid tumors. Clin. Cancer Res. 15, 1923–1930 (2009).
Reddy, A. T. et al. Efficacy of high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumor: a report from the Children’s Oncology Group Trial ACNS0333. J. Clin. Oncol. 38, 1175–1185 (2020).
Wilson, B. G. et al. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 18, 316–328 (2010).
Wang, X. et al. BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors. Nat. Commun. 10, 1881 (2019).
Nakayama, R. T. et al. SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters. Nat. Genet. 49, 1613–1623 (2017).
Langer, L. F., Ward, J. M. & Archer, T. K. Tumor suppressor SMARCB1 suppresses super-enhancers to govern hESC lineage determination. eLife 8, e45672 (2019).
Jessa, S. et al. Stalled developmental programs at the root of pediatric brain tumors. Nat. Genet. 51, 1702–1713 (2019).
Cardoso-Moreira, M. et al. Gene expression across mammalian organ development. Nature 571, 505–509 (2019).
Lacomme, M., Liaubet, L., Pituello, F. & Bel-Vialar, S. NEUROG2 drives cell cycle exit of neuronal precursors by specifically repressing a subset of cyclins acting at the G1 and S phases of the cell cycle. Mol. Cell. Biol. 32, 2596–2607 (2012).
Bayat, H. et al. CRISPR/Cas9-mediated deletion of a GA-repeat in human GPM6B leads to disruption of neural cell differentiation from NT2 cells. Sci. Rep. 14, 2136 (2024).
Jovanovic, V. M. et al. A defined roadmap of radial glia and astrocyte differentiation from human pluripotent stem cells. Stem Cell Rep. 18, 1701–1720 (2023).
Chuang, Y. Y. et al. Role of synaptojanin 2 in glioma cell migration and invasion. Cancer Res. 64, 8271–8275 (2004).
Wang, X. et al. SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation. Nat. Genet. 49, 289–295 (2017).
Domcke, S. et al. A human cell atlas of fetal chromatin accessibility. Science 370, eaba7612 (2020).
Zhang, K. et al. A single-cell atlas of chromatin accessibility in the human genome. Cell 184, 5985–6001.e19 (2021).
Moore, J. E. et al. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583, 699–710 (2020).
Zhao, B. et al. Znhit1 controls intestinal stem cell maintenance by regulating H2A.Z incorporation. Nat. Commun. 10, 1071 (2019).
Viner-Breuer, R., Yilmaz, A., Benvenisty, N. & Goldberg, M. The essentiality landscape of cell cycle related genes in human pluripotent and cancer cells. Cell Div. 14, 15 (2019).
Divvela, S. S. K., Saberi, D. & Brand-Saberi, B. Atoh8 in development and disease. Biology 11, 136 (2022).
Valdés-Mora, F. et al. Acetylation of H2A.Z is a key epigenetic modification associated with gene deregulation and epigenetic remodeling in cancer. Genome Res. 22, 307–321 (2012).
Mimitou, E. P. et al. Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells. Nat. Biotechnol. 39, 1246–1258 (2021).
Sanson, K. R. et al. Optimized libraries for CRISPR–Cas9 genetic screens with multiple modalities. Nat. Commun. 9, 5416 (2018).
Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 10–12 (2011).
Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
Picelli, S. et al. Tn5 transposase and tagmentation procedures for massively scaled sequencing projects. Genome Res. 24, 2033–2040 (2014).
Corces, M. R. et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14, 959–962 (2017).
Xu, W. et al. ISSAAC-seq enables sensitive and flexible multimodal profiling of chromatin accessibility and gene expression in single cells. Nat. Methods 19, 1243–1249 (2022).
Nørholm, M. H. H. A mutant Pfu DNA polymerase designed for advanced uracil-excision DNA engineering. BMC Biotechnol. 10, 21 (2010).
Grandi, F. C., Modi, H., Kampman, L. & Corces, M. R. Chromatin accessibility profiling by ATAC-seq. Nat. Protoc. 17, 1518–1552 (2022).
Preissl, S. et al. Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation. Nat. Neurosci. 21, 432–439 (2018).
Adey, A. C. Tagmentation-based single-cell genomics. Genome Res. 31, 1693–1705 (2021).
Replogle, J. M. et al. Combinatorial single-cell CRISPR screens by direct guide RNA capture and targeted sequencing. Nat. Biotechnol. 38, 954–961 (2020).
Zhu, Y. Y., Machleder, E. M., Chenchik, A., Li, R. & Siebert, P. D. Reverse transcriptase template switching: a SMART approach for full-length cDNA library construction. Biotechniques 30, 892–897 (2001).
Picelli, S. et al. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171–181 (2014).
Bagnoli, J. W. et al. Sensitive and powerful single-cell RNA sequencing using mcSCRB-seq. Nat. Commun. 9, 2937 (2018).
Di, L. et al. RNA sequencing by direct tagmentation of RNA/DNA hybrids. Proc. Natl Acad. Sci. USA 117, 2886–2893 (2020).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Zhang, Y. et al. Model-based analysis of ChIP-seq (MACS). Genome Biol. 9, R137 (2008).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
Griffiths, J. A., Richard, A. C., Bach, K., Lun, A. T. L. & Marioni, J. C. Detection and removal of barcode swapping in single-cell RNA-seq data. Nat. Commun. 9, 2667 (2018).
Amezquita, R. A. et al. Orchestrating single-cell analysis with Bioconductor. Nat. Methods 17, 137–145 (2020).
Levenshtein, V. I. Binary codes capable of correcting deletions, insertions, and reversals. Sov. Phys. Dokl. 10, 707–710 (1966).
Barry, T., Mason, K., Roeder, K. & Katsevich, E. Robust differential expression testing for single-cell CRISPR screens at low multiplicity of infection. Genome Biol. 25, 124 (2024).
Xu, S. et al. Using clusterProfiler to characterize multiomics data. Nat. Protoc. https://doi.org/10.1038/s41596-024-01020-z (2024).
Skene, P. J. & Henikoff, S. An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. eLife 6, e21856 (2017).
Tarasov, A., Vilella, A. J., Cuppen, E., Nijman, I. J. & Prins, P. Sambamba: fast processing of NGS alignment formats. Bioinformatics 31, 2032–2034 (2015).
Riemondy, K. et al. valr: reproducible genome interval analysis in R. F1000Res. 6, 1025 (2017).
Ramírez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).
Dharia, N. V. et al. A first-generation pediatric cancer dependency map. Nat. Genet. 53, 529–538 (2021).
Amemiya, H. M., Kundaje, A. & Boyle, A. P. The ENCODE blacklist: identification of problematic regions of the genome. Sci. Rep. 9, 9354 (2019).
Fiskin, E. et al. Single-cell profiling of proteins and chromatin accessibility using PHAGE-ATAC. Nat. Biotechnol. 40, 374–381 (2022).
Stirling, D. R. et al. CellProfiler 4: improvements in speed, utility and usability. BMC Bioinformatics 22, 433 (2021).
