{"entity": "researcher", "timestamp": "2026-10-13T19:29:09.898Z", "family": "Sanjana", "given": "Neville E", "initials": "NE", "orcid": "0000-0002-1504-0027", "affiliations": ["New York Genome Center, New York, NY 10013, USA.", "Department of Biology, New York University, New York, NY 10003, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/fee65a1527cc49e2942d946fba4ded65.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/fee65a1527cc49e2942d946fba4ded65"}}, "publications": [{"entity": "publication", "iuid": "0cdd265652aa4f389e3bace451468221", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0cdd265652aa4f389e3bace451468221.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0cdd265652aa4f389e3bace451468221"}}, "title": "Nonlinear transcriptional responses to gradual modulation of transcription factor dosage.", "authors": [{"family": "Domingo", "given": "J\u00falia", "initials": "J", "orcid": "0000-0001-6359-2785", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c038c148261945cc8b4c0bd09c99b4e0.json"}}, {"family": "Minaeva", "given": "Mariia", "initials": "M", "orcid": "0000-0001-7028-1264", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c146bcfb925444b78cab53b61cf912e2.json"}}, {"family": "Morris", "given": "John A", "initials": "JA", "orcid": "0000-0003-2769-8202", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61b4dd70c06748a2abd7aa2a73200b40.json"}}, {"family": "Ghatan", "given": "Samuel", "initials": "S"}, {"family": "Ziosi", "given": "Marcello", "initials": "M", "orcid": "0000-0001-5128-6158", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b75170862b824a698666eb8d3938d581.json"}}, {"family": "Sanjana", "given": "Neville E", "initials": "NE", "orcid": "0000-0002-1504-0027", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fee65a1527cc49e2942d946fba4ded65.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}], "type": "journal article", "published": "2026-01-14", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "13", "issn-l": "2050-084X"}, "abstract": "Genomic loci associated with common traits and diseases are typically non-coding and likely impact gene expression, sometimes coinciding with rare loss-of-function variants in the target gene. However, our understanding of how gradual changes in gene dosage affect molecular, cellular, and organismal traits is currently limited. To address this gap, we induced gradual changes in gene expression of four genes using CRISPR activation and inactivation in human-derived K562 cells. Downstream transcriptional consequences of dosage modulation of three master trans-regulators associated with blood cell traits (GFI1B, NFE2, and MYB) were examined using targeted single-cell multimodal sequencing. We showed that guide tiling around the TSS is the most effective way to modulate cis gene expression across a wide range of fold changes, with further effects from chromatin accessibility and histone marks that differ between the inhibition and activation systems. Our single-cell data allowed us to precisely detect subtle to large gene expression changes in dozens of trans genes, revealing that many responses to dosage changes of these three TFs are nonlinear, including non-monotonic behaviours, even when constraining the fold changes of the master regulators to a copy number gain or loss. We found that the dosage properties are linked to gene constraint and that some of these nonlinear responses are enriched for disease and GWAS genes. Overall, our study provides a straightforward and scalable method to precisely modulate gene expression and gain insights into its downstream consequences at high resolution.", "doi": "10.7554/eLife.100555", "pmid": "41532405", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12803512"}, {"db": "pii", "key": "100555"}, {"db": "GEO", "key": "GSE257547"}], "notes": [], "created": "2026-08-20T13:50:49.996Z", "modified": "2026-09-23T14:12:02.213Z"}, {"entity": "publication", "iuid": "2ab4b223c10c4511b4e636c080ec13cc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2ab4b223c10c4511b4e636c080ec13cc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2ab4b223c10c4511b4e636c080ec13cc"}}, "title": "Nonlinear transcriptional responses to gradual modulation of transcription factor dosage", "authors": [{"family": "Domingo", "given": "J\u00falia", "initials": "J", "orcid": "0000-0001-6359-2785", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c038c148261945cc8b4c0bd09c99b4e0.json"}}, {"family": "Minaeva", "given": "Mariia", "initials": "M", "orcid": "0000-0001-7028-1264", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c146bcfb925444b78cab53b61cf912e2.json"}}, {"family": "Morris", "given": "John A", "initials": "JA", "orcid": "0000-0003-2769-8202", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61b4dd70c06748a2abd7aa2a73200b40.json"}}, {"family": "Ghatan", "given": "Samuel", "initials": "S"}, {"family": "Ziosi", "given": "Marcello", "initials": "M", "orcid": "0000-0001-5128-6158", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b75170862b824a698666eb8d3938d581.json"}}, {"family": "Sanjana", "given": "Neville E", "initials": "NE", "orcid": "0000-0002-1504-0027", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fee65a1527cc49e2942d946fba4ded65.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}], "type": "posted-content", "published": "2025-11-25", "journal": {"issn-l": null}, "abstract": null, "doi": "10.7554/elife.100555.2", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T13:50:54.071Z", "modified": "2026-09-23T14:54:37.567Z"}, {"entity": "publication", "iuid": "7b3e9f824f464167aec23b08c33edda4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7b3e9f824f464167aec23b08c33edda4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7b3e9f824f464167aec23b08c33edda4"}}, "title": "Nonlinear transcriptional responses to gradual modulation of transcription factor dosage.", "authors": [{"family": "Domingo", "given": "J\u00falia", "initials": "J", "orcid": "0000-0001-6359-2785", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c038c148261945cc8b4c0bd09c99b4e0.json"}}, {"family": "Minaeva", "given": "Mariia", "initials": "M", "orcid": "0000-0001-7028-1264", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c146bcfb925444b78cab53b61cf912e2.json"}}, {"family": "Morris", "given": "John A", "initials": "JA", "orcid": "0000-0003-2769-8202", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61b4dd70c06748a2abd7aa2a73200b40.json"}}, {"family": "Ghatan", "given": "Samuel", "initials": "S"}, {"family": "Ziosi", "given": "Marcello", "initials": "M", "orcid": "0000-0001-5128-6158", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b75170862b824a698666eb8d3938d581.json"}}, {"family": "Sanjana", "given": "Neville E", "initials": "NE", "orcid": "0000-0002-1504-0027", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fee65a1527cc49e2942d946fba4ded65.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}], "type": "journal article", "published": "2025-08-07", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "Genomic loci associated with common traits and diseases are typically non-coding and likely impact gene expression, sometimes coinciding with rare loss-of-function variants in the target gene. However, our understanding of how gradual changes in gene dosage affect molecular, cellular, and organismal traits is currently limited. To address this gap, we induced gradual changes in gene expression of four genes using CRISPR activation and inactivation. Downstream transcriptional consequences of dosage modulation of three master trans-regulators associated with blood cell traits (GFI1B, NFE2, and MYB) were examined using targeted single-cell multimodal sequencing. We showed that guide tiling around the TSS is the most effective way to modulate cis gene expression across a wide range of fold-changes, with further effects from chromatin accessibility and histone marks that differ between the inhibition and activation systems. Our single-cell data allowed us to precisely detect subtle to large gene expression changes in dozens of trans genes, revealing that many responses to dosage changes of these three TFs are nonlinear, including non-monotonic behaviours, even when constraining the fold-changes of the master regulators to a copy number gain or loss. We found that the dosage properties are linked to gene constraint and that some of these nonlinear responses are enriched for disease and GWAS genes. Overall, our study provides a straightforward and scalable method to precisely modulate gene expression and gain insights into its downstream consequences at high resolution.", "doi": "10.1101/2024.03.01.582837", "pmid": "38464330", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10925300"}, {"db": "pii", "key": "2024.03.01.582837"}], "notes": [], "created": "2026-08-20T10:52:31.753Z", "modified": "2026-09-23T13:46:33.035Z"}, {"entity": "publication", "iuid": "2c08842d2ad0418a8807a686f340dab1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2c08842d2ad0418a8807a686f340dab1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2c08842d2ad0418a8807a686f340dab1"}}, "title": "Non-linear transcriptional responses to gradual modulation of transcription factor dosage", "authors": [{"family": "Domingo", "given": "J\u00falia", "initials": "J", "orcid": "0000-0001-6359-2785", "researcher": {"href": 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"https://publications-affiliated.scilifelab.se/researcher/fee65a1527cc49e2942d946fba4ded65.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}], "type": "posted-content", "published": "2024-12-17", "journal": {"issn-l": null}, "abstract": null, "doi": "10.7554/elife.100555.1", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T13:50:52.021Z", "modified": "2026-09-23T14:22:17.283Z"}, {"entity": "publication", "iuid": "ef2cb8b1593a430c801592f22e77d239", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ef2cb8b1593a430c801592f22e77d239.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ef2cb8b1593a430c801592f22e77d239"}}, "title": "Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens.", "authors": [{"family": "Morris", "given": "John A", "initials": "JA", "orcid": "0000-0003-2769-8202", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61b4dd70c06748a2abd7aa2a73200b40.json"}}, {"family": "Caragine", "given": "Christina", "initials": "C", "orcid": "0000-0002-5958-7200", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c732d11aac374c009efc62db0d1f10f7.json"}}, {"family": "Daniloski", "given": "Zharko", "initials": "Z", "orcid": "0000-0002-3453-0849", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bceaca798dad4c7581e4e73d7d9f3ba3.json"}}, {"family": "Domingo", "given": "J\u00falia", "initials": "J"}, {"family": "Barry", "given": "Timothy", "initials": "T"}, {"family": "Lu", "given": "Lu", "initials": "L", "orcid": "0000-0002-7343-7161", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e095d4dff1047caa95c3caf5419afe4.json"}}, {"family": "Davis", "given": "Kyrie", "initials": "K"}, {"family": "Ziosi", "given": "Marcello", "initials": "M"}, {"family": "Glinos", "given": "Dafni A", "initials": "DA", "orcid": "0000-0001-5556-0222", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1486a4c3b11d4ed1b9f2b41f237df923.json"}}, {"family": "Hao", "given": "Stephanie", "initials": "S"}, {"family": "Mimitou", "given": "Eleni P", "initials": "EP", "orcid": "0000-0001-9737-6394", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c6a8bf865c1406aa7f8430537c2c24f.json"}}, {"family": "Smibert", "given": "Peter", "initials": "P", "orcid": "0000-0003-0772-1647", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d10d292aa07b4fd0993508d7b9eeb8c7.json"}}, {"family": "Roeder", "given": "Kathryn", "initials": "K", "orcid": "0000-0002-8869-6254", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8d6738b5d7d497a8718941b4acc3b91.json"}}, {"family": "Katsevich", "given": "Eugene", "initials": "E", "orcid": "0000-0003-0598-2050", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b26c1c34a2c44f585f8d5b94eaeadf8.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}, {"family": "Sanjana", "given": "Neville E", "initials": "NE", "orcid": "0000-0002-1504-0027", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fee65a1527cc49e2942d946fba4ded65.json"}}], "type": "journal article", "published": "2023-05-19", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "380", "issue": "6646", "pages": "eadh7699", "issn-l": "0036-8075"}, "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.", "doi": "10.1126/science.adh7699", "pmid": "37141313", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1931649"}, {"db": "pmc", "key": "PMC10518238"}], "notes": [], "created": "2026-10-01T08:23:10.497Z", "modified": "2026-10-01T08:23:10.941Z"}]}