{"entity": "researcher", "timestamp": "2026-08-20T21:14:51.471Z", "family": "MacArthur", "given": "Daniel G", "initials": "DG", "orcid": "0000-0002-5771-2290", "affiliations": ["Medical and Population Genetics Program, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.", "Centre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, Sydney, New South Wales, Australia.", "Centre for Population Genomics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/5458d63cd0e04ba490ef7d662be857b8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/5458d63cd0e04ba490ef7d662be857b8"}}, "publications": [{"entity": "publication", "iuid": "b129b7a43ac94cf583edf1d30ced5e37", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b129b7a43ac94cf583edf1d30ced5e37.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b129b7a43ac94cf583edf1d30ced5e37"}}, "title": "Transcriptome variation in human tissues revealed by long-read sequencing.", "authors": [{"family": "Glinos", "given": "Dafni A", "initials": "DA", "orcid": "0000-0001-5556-0222", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1486a4c3b11d4ed1b9f2b41f237df923.json"}}, {"family": "Garborcauskas", "given": "Garrett", "initials": "G", "orcid": "0000-0003-0316-461X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1ce65ab6a90424a96e86b48257b7ec4.json"}}, {"family": "Hoffman", "given": "Paul", "initials": "P", "orcid": "0000-0002-7693-8957", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d896695f142645a5883ecfa727c11982.json"}}, {"family": "Ehsan", "given": "Nava", "initials": "N"}, {"family": "Jiang", "given": "Lihua", "initials": "L"}, {"family": "Gokden", "given": "Alper", "initials": "A", "orcid": "0000-0002-9659-7352", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/20ce8da5b9394fa99e5a3da05f0215e7.json"}}, {"family": "Dai", "given": "Xiaoguang", "initials": "X"}, {"family": "Aguet", "given": "Fran\u00e7ois", "initials": "F", "orcid": "0000-0001-9414-300X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d39672f853614eaea6736b74d2e2ebd9.json"}}, {"family": "Brown", "given": "Kathleen L", "initials": "KL"}, {"family": "Garimella", "given": "Kiran", "initials": "K"}, {"family": "Bowers", "given": "Tera", "initials": "T"}, {"family": "Costello", "given": "Maura", "initials": "M"}, {"family": "Ardlie", "given": "Kristin", "initials": "K"}, {"family": "Jian", "given": "Ruiqi", "initials": "R", "orcid": "0000-0003-2406-5303", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2881b56dc8b14f6caba545539d291a78.json"}}, {"family": "Tucker", "given": "Nathan R", "initials": "NR"}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd1830794e884e6e849fd4f7645c9b61.json"}}, {"family": "Harrington", "given": "Eoghan D", "initials": "ED"}, {"family": "Tang", "given": "Hua", "initials": "H", "orcid": "0000-0002-0177-8864", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b94bfdf4a6ec48c6af4dcc4da26c7c7e.json"}}, {"family": "Snyder", "given": "Michael", "initials": "M", "orcid": "0000-0003-0784-7987", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ce9e294ff3b64f7caa770c883d12514c.json"}}, {"family": "Juul", "given": "Sissel", "initials": "S", "orcid": "0000-0002-0315-4449", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/11abdf8aade74d3d83d52d8a2f2a373c.json"}}, {"family": "Mohammadi", "given": "Pejman", "initials": "P"}, {"family": "MacArthur", "given": "Daniel G", "initials": "DG", "orcid": "0000-0002-5771-2290", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5458d63cd0e04ba490ef7d662be857b8.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}, {"family": "Cummings", "given": "Beryl B", "initials": "BB", "orcid": "0000-0001-6346-1646", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b7d7db3f43184401919033f3dff79c10.json"}}], "type": "journal article", "published": "2022-08-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "608", "issue": "7922", "pages": "353-359", "issn-l": "0028-0836"}, "abstract": "Regulation of transcript structure generates transcript diversity and plays an important role in human disease1-7. The advent of long-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure8-16. In this Article, we present a large human long-read RNA-seq dataset using the Oxford Nanopore Technologies platform from 88 samples from Genotype-Tissue Expression (GTEx) tissues and cell lines, complementing the GTEx resource. We identified just over 70,000 novel transcripts for annotated genes, and validated the protein expression of 10% of novel transcripts. We developed a new computational package, LORALS, to analyse the genetic effects of rare and common variants on the transcriptome by allele-specific analysis of long reads. We characterized allele-specific expression and transcript structure events, providing new insights into the specific transcript alterations caused by common and rare genetic variants and highlighting the resolution gained from long-read data. We were able to perturb the transcript structure upon knockdown of PTBP1, an RNA binding protein that mediates splicing, thereby finding genetic regulatory effects that are modified by the cellular environment. Finally, we used this dataset to enhance variant interpretation and study rare variants leading to aberrant splicing patterns.", "doi": "10.1038/s41586-022-05035-y", "pmid": "35922509", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1877316"}, {"db": "pmc", "key": "PMC10337767"}, {"db": "pii", "key": "10.1038/s41586-022-05035-y"}], "notes": [], "created": "2026-08-20T08:57:46.247Z", "modified": "2026-08-20T08:57:46.697Z"}, {"entity": "publication", "iuid": "6e3559759a344c46a0e70ccefc380d8e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6e3559759a344c46a0e70ccefc380d8e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6e3559759a344c46a0e70ccefc380d8e"}}, "title": "From variant to function in human disease genetics.", "authors": [{"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}, {"family": "MacArthur", "given": "Daniel G", "initials": "DG", "orcid": "0000-0002-5771-2290", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5458d63cd0e04ba490ef7d662be857b8.json"}}], "type": "journal article", "published": "2021-09-24", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "373", "issue": "6562", "pages": "1464-1468", "issn-l": "0036-8075"}, "abstract": "Over the next decade, the primary challenge in human genetics will be to understand the biological mechanisms by which genetic variants influence phenotypes, including disease risk. Although the scale of this challenge is daunting, better methods for functional variant interpretation will have transformative consequences for disease diagnosis, risk prediction, and the development of new therapies. An array of new methods for characterizing variant impact at scale, using patient tissue samples as well as in vitro models, are already being applied to dissect variant mechanisms across a range of human cell types and environments. These approaches are also increasingly being deployed in clinical settings. We discuss the rationale, approaches, applications, and future outlook for characterizing the molecular and cellular effects of genetic variants.", "doi": "10.1126/science.abi8207", "pmid": "34554789", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:59:32.267Z", "modified": "2026-08-20T11:59:32.361Z"}]}