{"entity": "researcher", "timestamp": "2026-08-13T18:11:06.641Z", "family": "Paten", "given": "Benedict", "initials": "B", "orcid": "0000-0001-8863-3539", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/956ebe9c0b6e43d7ac2a568519f43431.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/956ebe9c0b6e43d7ac2a568519f43431"}}, "publications": [{"entity": "publication", "iuid": "88402be877d840f287560915f38fb419", "links": {"self": {"href": "https://publications.scilifelab.se/publication/88402be877d840f287560915f38fb419.json"}, "display": {"href": "https://publications.scilifelab.se/publication/88402be877d840f287560915f38fb419"}}, "title": "Identification of constrained sequence elements across 239 primate genomes.", "authors": [{"family": "Kuderna", "given": "Lukas F K", "initials": "LFK", "orcid": "0000-0002-9992-9295", "researcher": {"href": 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"initials": "F"}, {"family": "Wu", "given": "Dongdong", "initials": "D", "orcid": "0000-0001-7101-7297", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3c04b15c01f426c9aefa1d354686924.json"}}, {"family": "Zhou", "given": "Long", "initials": "L", "orcid": "0000-0001-7596-2691", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b94d99a7bd94f708263be63bb1213de.json"}}, {"family": "Shao", "given": "Yong", "initials": "Y", "orcid": "0000-0003-1704-8425", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3d2a9ee5cad460b9526e5e0949a4971.json"}}, {"family": "Zhang", "given": "Guojie", "initials": "G"}, {"family": "Keyyu", "given": "Julius D", "initials": "JD"}, {"family": "Knauf", "given": "Sascha", "initials": "S", "orcid": "0000-0001-5744-4946", "researcher": {"href": "https://publications.scilifelab.se/researcher/19e7421c27d54306af67de01898514e1.json"}}, {"family": "Le", "given": "Minh D", "initials": "MD"}, {"family": 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{"href": "https://publications.scilifelab.se/researcher/c14600c4e0d54a7aae393c728d9af088.json"}}, {"family": "Melin", "given": "Amanda D", "initials": "AD", "orcid": "0000-0002-0612-2514", "researcher": {"href": "https://publications.scilifelab.se/researcher/575c577a54f945208b48ac7a7bfb3089.json"}}, {"family": "Guschanski", "given": "Katerina", "initials": "K", "orcid": "0000-0002-8493-5457", "researcher": {"href": "https://publications.scilifelab.se/researcher/84b8b0757f02429b9bd419acb42ab6a3.json"}}, {"family": "Schierup", "given": "Mikkel Heide", "initials": "MH", "orcid": "0000-0002-5028-1790", "researcher": {"href": "https://publications.scilifelab.se/researcher/804667e7b8ac476abc214d98a39cb693.json"}}, {"family": "Beck", "given": "Robin M D", "initials": "RMD", "orcid": "0000-0002-7050-7072", "researcher": {"href": "https://publications.scilifelab.se/researcher/080d300c5b974a03a3c9244c717608f6.json"}}, {"family": "Karakikes", "given": "Ioannis", "initials": "I"}, {"family": "Wang", "given": "Kevin C", "initials": "KC"}, {"family": "Umapathy", "given": "Govindhaswamy", "initials": "G", "orcid": "0000-0003-4086-7445", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfdccc5f3a744d0282348e8970a2bda3.json"}}, {"family": "Roos", "given": "Christian", "initials": "C", "orcid": "0000-0003-0190-4266", "researcher": {"href": "https://publications.scilifelab.se/researcher/23a5f8f0f0ba42858ce4c395ab285535.json"}}, {"family": "Boubli", "given": "Jean P", "initials": "JP", "orcid": "0000-0002-5833-9264", "researcher": {"href": "https://publications.scilifelab.se/researcher/1550f83d88314bfdaabb6e5fcfaf70f0.json"}}, {"family": "Siepel", "given": "Adam", "initials": "A", "orcid": "0000-0002-3557-7219", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3448669c691448880dcef78e3376434.json"}}, {"family": "Kundaje", "given": "Anshul", "initials": "A"}, {"family": "Paten", "given": "Benedict", "initials": "B", "orcid": "0000-0001-8863-3539", "researcher": {"href": "https://publications.scilifelab.se/researcher/956ebe9c0b6e43d7ac2a568519f43431.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Rogers", "given": "Jeffrey", "initials": "J", "orcid": "0000-0002-7374-6490", "researcher": {"href": "https://publications.scilifelab.se/researcher/18b3aaf283e443feb46f08e2aba6dc3d.json"}}, {"family": "Marques Bonet", "given": "Tomas", "initials": "T", "orcid": "0000-0002-5597-3075", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4ea50a4fe3147f3b979ccaa8a2a0de4.json"}}, {"family": "Farh", "given": "Kyle Kai-How", "initials": "KK", "orcid": "0000-0001-6947-8537", "researcher": {"href": "https://publications.scilifelab.se/researcher/9114a66f84da4c8f85360fb8606354c6.json"}}], "type": "journal article", "published": "2023-11-29", "journal": {"title": "Nature", "issn": "1476-4687", "issn-l": "0028-0836"}, "abstract": "Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3-9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.", "doi": "10.1038/s41586-023-06798-8", "pmid": "38030727", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-023-06798-8"}], "notes": [], "created": "2023-12-18T15:03:31.119Z", "modified": "2024-01-16T13:48:31.631Z"}, {"entity": "publication", "iuid": "6cea0eb350cd40bba54717d8b627da6b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6cea0eb350cd40bba54717d8b627da6b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6cea0eb350cd40bba54717d8b627da6b"}}, "title": "Leveraging base-pair mammalian constraint to understand genetic variation and human disease.", "authors": [{"family": "Sullivan", "given": "Patrick F", "initials": "PF", "orcid": "0000-0002-6619-873X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d95de0b5ab14586980a6a13c8299346.json"}}, {"family": "Meadows", "given": "Jennifer R S", "initials": "JRS", "orcid": "0000-0002-0850-230X", "researcher": {"href": "https://publications.scilifelab.se/researcher/86acdca0104c4552880d5a7cb5ac6565.json"}}, {"family": "Gazal", "given": "Steven", "initials": "S", "orcid": "0000-0003-4510-5730", "researcher": {"href": "https://publications.scilifelab.se/researcher/fecc8307017145088589536e3c312515.json"}}, {"family": "Phan", "given": "BaDoi N", "initials": "BN", "orcid": "0000-0001-6331-5980", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9e37df4e5c54204a19ea394e1f7651e.json"}}, {"family": "Li", "given": "Xue", "initials": "X", "orcid": "0000-0002-9126-2692", "researcher": {"href": "https://publications.scilifelab.se/researcher/bfa777bbc9d34c0e9f4920decc7cdcb3.json"}}, {"family": "Genereux", "given": "Diane P", "initials": "DP", "orcid": "0000-0001-5770-0989", "researcher": {"href": "https://publications.scilifelab.se/researcher/0dedda53aab044eabd09ae377084ff9d.json"}}, {"family": "Dong", "given": "Michael X", "initials": "MX", "orcid": "0000-0003-4084-3099", "researcher": {"href": "https://publications.scilifelab.se/researcher/d44d219b319346c481c82d69d5055cd8.json"}}, {"family": "Bianchi", "given": "Matteo", "initials": "M", "orcid": "0000-0003-3394-6495", "researcher": {"href": "https://publications.scilifelab.se/researcher/d645ef0e04a245f0ac9e7d7498b2bd69.json"}}, {"family": "Andrews", "given": "Gregory", "initials": "G", "orcid": "0000-0002-9880-3965", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f84c888473d45ea8d8e97945d508705.json"}}, {"family": "Sakthikumar", "given": "Sharadha", "initials": "S", "orcid": "0000-0002-7746-8264", "researcher": {"href": "https://publications.scilifelab.se/researcher/538c86311b2549d6a5214a5562578cc2.json"}}, {"family": "Nordin", "given": "Jessika", "initials": "J", "orcid": 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"https://publications.scilifelab.se/researcher/956ebe9c0b6e43d7ac2a568519f43431.json"}}, {"family": "Reilly", "given": "Steven K", "initials": "SK", "orcid": "0000-0003-3140-1483", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c12bcf707394bb5b9c34075aba19f13.json"}}, {"family": "Hughes", "given": "Graham M", "initials": "GM", "orcid": "0000-0003-3088-345X", "researcher": {"href": "https://publications.scilifelab.se/researcher/800da869332a45b9b4c7bd8fd5522666.json"}}, {"family": "Weng", "given": "Zhiping", "initials": "Z", "orcid": "0000-0002-3032-7966", "researcher": {"href": "https://publications.scilifelab.se/researcher/25ad44250cba4b0cba5250b07f764ba3.json"}}, {"family": "Pollard", "given": "Katherine S", "initials": "KS", "orcid": "0000-0002-9870-6196", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb2a865a28524f55bb5d9df3db79563f.json"}}, {"family": "Pfenning", "given": "Andreas R", "initials": "AR", "orcid": "0000-0002-3447-9801", "researcher": {"href": "https://publications.scilifelab.se/researcher/579e32fe57da4d738b7fbf0a57fb6faf.json"}}, {"family": "Forsberg-Nilsson", "given": "Karin", "initials": "K", "orcid": "0000-0003-0692-6245", "researcher": {"href": "https://publications.scilifelab.se/researcher/5da04859250141a0a7271a69c7da9176.json"}}, {"family": "Karlsson", "given": "Elinor K", "initials": "EK", "orcid": "0000-0002-4343-3776", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bd97378a1cc403db0923895adde15e3.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}], "type": "journal article", "published": "2023-04-28", "journal": {"title": "Science", "issn": "1095-9203", "issn-l": "0036-8075", "volume": "380", "issue": "6643", "pages": "eabn2937"}, "abstract": "Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.", "doi": "10.1126/science.abn2937", "pmid": "37104612", "labels": {"NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1897004"}, {"db": "pmc", "key": "PMC10259825"}], "notes": [], "created": "2023-12-01T08:54:10.456Z", "modified": "2024-01-16T13:48:33.619Z"}, {"entity": "publication", "iuid": "d7e4da3ff4c54966b53e2e1210128441", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d7e4da3ff4c54966b53e2e1210128441.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d7e4da3ff4c54966b53e2e1210128441"}}, "title": "Evolutionary constraint and innovation across hundreds of placental mammals.", "authors": 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"type": "journal article", "published": "2023-04-28", "journal": {"title": "Science", "issn": "1095-9203", "issn-l": "0036-8075", "volume": "380", "issue": "6643", "pages": "eabn3943"}, "abstract": "Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.", "doi": "10.1126/science.abn3943", "pmid": "37104599", "labels": {"NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1896905"}, {"db": "pmc", "key": "PMC10250106"}], "notes": [], "created": "2023-12-01T08:40:50.036Z", "modified": "2024-01-16T13:48:33.655Z"}, {"entity": "publication", "iuid": "0cd1833de8764e41812f14260f5961b5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0cd1833de8764e41812f14260f5961b5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0cd1833de8764e41812f14260f5961b5"}}, "title": "Dense sampling of bird diversity increases power of comparative genomics.", "authors": [{"family": 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"researcher": {"href": "https://publications.scilifelab.se/researcher/8c77b745d8b044d4aed9478d056be226.json"}}, {"family": "Haussler", "given": "David", "initials": "D", "orcid": "0000-0003-1533-4575", "researcher": {"href": "https://publications.scilifelab.se/researcher/de140026a4f24291be768e713e4881bb.json"}}, {"family": "Li", "given": "Qiye", "initials": "Q", "orcid": "0000-0002-5993-0312", "researcher": {"href": "https://publications.scilifelab.se/researcher/d807a3a13669425c9b00e4a2b7db672a.json"}}, {"family": "Yang", "given": "Huanming", "initials": "H"}, {"family": "Wang", "given": "Jian", "initials": "J"}, {"family": "Lei", "given": "Fumin", "initials": "F"}, {"family": "Rahbek", "given": "Carsten", "initials": "C"}, {"family": "Gilbert", "given": "M Thomas P", "initials": "MTP", "orcid": "0000-0002-5805-7195", "researcher": {"href": "https://publications.scilifelab.se/researcher/873e2383b99a43d7848bf387264cf0e8.json"}}, {"family": "Graves", "given": "Gary R", "initials": "GR", "orcid": "0000-0003-1406-5246", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc3b9edee185456d971f5b596c3086fe.json"}}, {"family": "Jarvis", "given": "Erich D", "initials": "ED", "orcid": "0000-0001-8931-5049", "researcher": {"href": "https://publications.scilifelab.se/researcher/d565d5e1788e484d9d2da61af12f2120.json"}}, {"family": "Paten", "given": "Benedict", "initials": "B", "orcid": "0000-0001-8863-3539", "researcher": {"href": "https://publications.scilifelab.se/researcher/956ebe9c0b6e43d7ac2a568519f43431.json"}}, {"family": "Zhang", "given": "Guojie", "initials": "G", "orcid": "0000-0001-6860-1521", "researcher": {"href": "https://publications.scilifelab.se/researcher/62f3c7981a1c43909817e72519232ff8.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "587", "issue": "7833", "pages": "252-257", "issn-l": "0028-0836"}, "abstract": "Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.", "doi": "10.1038/s41586-020-2873-9", "pmid": "33177665", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-020-2873-9"}, {"db": "pmc", "key": "PMC7759463"}], "notes": [], "created": "2020-12-07T16:36:44.079Z", "modified": "2021-11-10T12:45:51.851Z"}]}