{"entity": "researcher", "timestamp": "2026-08-20T20:40:48.463Z", "family": "Hoffman", "given": "Paul", "initials": "P", "orcid": "0000-0002-7693-8957", "affiliations": ["New York Genome Center, New York, NY, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/d896695f142645a5883ecfa727c11982.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/d896695f142645a5883ecfa727c11982"}}, "publications": [{"entity": "publication", "iuid": "5470ece56a8c4dbc9d952ed9283ec96a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5470ece56a8c4dbc9d952ed9283ec96a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5470ece56a8c4dbc9d952ed9283ec96a"}}, "title": "Improved Identification of Large-effect Rare Genetic Variants using Haplotype Aggregated Allele-specific Expression Data.", "authors": [{"family": "Ganapathy", "given": "Kaushik Ram", "initials": "KR", "orcid": "0000-0002-2439-9373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a3cbe7b6c96a4a11bcc196a4a6541fe7.json"}}, {"family": "Broly", "given": "Martin", "initials": "M", "orcid": "0009-0005-4685-7063", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4b30cd1040b44cd1b66c34990b8c5c22.json"}}, {"family": "Silverstein", "given": "Sarah", "initials": "S", "orcid": "0000-0003-3428-3734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2a1ba93ff73044b0ba5ea8ba189d4b32.json"}}, {"family": "Mendoza", "given": "Marcela", "initials": "M"}, {"family": "Song", "given": "Eric", "initials": "E"}, {"family": "Kotis", "given": "Bence", "initials": "B"}, {"family": "Hoffman", "given": "Paul", "initials": "P", "orcid": "0000-0002-7693-8957", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d896695f142645a5883ecfa727c11982.json"}}, {"family": "PCGC Consortium", "given": "", "initials": ""}, {"family": "Torkamani", "given": "Ali", "initials": "A", "orcid": "0000-0003-0232-8053", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ae21020e98743268624f071d67ff59e.json"}}, {"family": "Adams", "given": "David R", "initials": "DR", "orcid": "0000-0002-6660-1242", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d21d5473e6b4d479919dee26040fed5.json"}}, {"family": "Bonnemann", "given": "Carsten", "initials": "C", "orcid": "0000-0002-5930-2324", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7c497515eaf440eb5ffa0e64b3b7c58.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T", "orcid": "0000-0002-7746-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8401dbf3ffb4f35bcc8e16f4a04cd7c.json"}}, {"family": "Mohammadi", "given": "Pejman", "initials": "P", "orcid": "0000-0003-2291-9272", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/01b7fe26479a4dd0b9be2ae8fe615daf.json"}}], "type": "journal article", "published": "2025-12-18", "journal": {"title": "medRxiv", "issn-l": null}, "abstract": "Allele-specific expression (ASE) outlier detection is a powerful tool for identifying genes affected by large effect rare genetic regulatory variants but suffers from data sparsity and noisy signal in low-count genes. Genome phasing can be utilized to aggregate ASE signal along haplotypes to alleviate both sparsity and noise. Yet statistical tools for utilizing haplotype-level ASE data for rare variant interpretation are lacking. Here, we present ANEVA-h, to quantify the amount of genetic variation in gene expression from haplotype-level ASE data in a population, enabling more accurate and comprehensive detection of regulatory effects. We apply ANEVA-h to GTEx project data, along with a compatible dosage outlier test, to show an over 2-fold increase in the number of testable genes, reduction of spurious outlier calls, and improved enrichment for rare high-impact variants. In clinical cohorts of neuromuscular and congenital heart disease, it enhances gene prioritization and identifies candidate diagnoses missed by DROP-MAE and ANEVA. Finally, we analyze globally diverse populations to characterize the impact of ancestry background in reference and the test population. We provide tools and data necessary to facilitate integration of haplotype level ASE outlier testing in rare variant interpretation pipelines.", "doi": "10.64898/2025.12.16.25341855", "pmid": "41445643", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12723776"}, {"db": "pii", "key": "2025.12.16.25341855"}], "notes": [], "created": "2026-08-20T13:48:39.712Z", "modified": "2026-08-20T13:49:38.482Z"}, {"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"}]}