Research

Research from the GREGoR Stanford Site

RNU4ATAC-opathy: Clinical, molecular and transcriptomic insights from a large cohort
Matalon DR, Duker AL, Arriaga TM, Russell K, Mendez HR, Bonner DE, Harley ME, Singer-Berk M, Wojcik MH, Pais L, DiTroia S, O'Leary M, Cassini T, Ezell K, Niehaus AD, Kaplan J, Wargowski DS, Smid CJ, Longenecker ED, Rodriguez Barreto AM, Miller DE, Keefe AC, Calderwood L, Enns GM, Tekin M, Bivona SA, Vora NL, Gilmore KL, Khan TN, Davis EE, Wang AW, Khan S, Maddirevula S, Al Abdi L, Abuyousef O, Shamseldin HE, Alkhalifi S, Abdulwahab F, Alqahtani M, Alhumaidi ZA, Nadeef S, Al Hashem AM, Bakur K, Faqeih EA, Abdalla E, Clarke A, Fletcher E, Keng WT, Ousager LB, de Silva DC, Haniffa M, Mari F, Lam W, Campbell J, Homfray T, Nampoothiri S, Li C, Chaudhari BP, Truxal K; Genomics Research to Elucidate the Genetics of Rare Diseases consortium, Undiagnosed Diseases Network; Bernstein JA, Montgomery SB, Wheeler MT, Alkuraya FS, O'Donnell-Luria A, Jackson AP, Campbell IM, Ganesh VS, Robertson N, Lemire G. Genet Med. 2026 Jun 19:102633. Epub ahead of print. PMID: 42322193

Population-scale detection of methylation outliers from long-read genome sequencing
Jensen TD, Kaur R, Bonner DE, Nguyen J, Reuter CM; Undiagnosed Diseases Network, Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium; Ashley EA, Bernstein JA, Wheeler MT, Montgomery SB. medRxiv [Preprint]. 2026 Jun 11:2026.06.09.26355279. PMID: 42326780

Bi-allelic RNU6ATAC variants cause a minor spliceopathy characterized by transcriptome-wide minor intron retention and multisystem manifestations
Mendez R, Arriaga TM, Ma J, Bonner DE, Emami S, Levy RJ, Alsagheir A, Alhaddad B, Bakur K, Ungar RA, Matalon DR, Miller AM, Nguyen J, Smith KS, Scott SA, Liao L, Ng Z, Marwaha S, Ward A; Undiagnosed Diseases Network; Genomics Research to Elucidate the Genetics of Rare Diseases Consortium; Novacic D, Alkuraya FS, Bernstein JA, Ganesh VS, O'Donnell-Luria A, Montgomery SB, Wheeler MT. HGG Adv. 2026 Apr 9;7(2):100588. PMID: 41808409

De Novo Variants Associated With Autosomal Recessive Conditions: Case Series and Implications for Genetic Testing and Counseling
Niehaus AD, Bonner DE, Carter J, Avello K, Jacob N, Neu MB, Mendez R, Qiao W, Scott SA, Levy RJ, Mattas L, Schymick J, Van Andel M, Muntoni F, Mueller J, Sarkozy A, DiTroia S, O'Leary M, Neale A, O'Donnell-Luria A, Toro C, Wolfe LA, Martinez-Agosto JA, Montgomery SB, Wheeler MT, Bernstein JA, Tise CG. Am J Med Genet A. 2026 Sep;200(9):2052-2060. PMID: 42002855

Biallelic variants in the noncoding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes
Rius R, Blakes AJM, Chen Y, De Jonghe J, Lecoquierre F, Dawes R, Cogne B, Kim HC, Alvi JR, Amblard F, Ansari M, Arlt A, Austin-Tse C, Baer S, Balasubramanian M, Balton EV, Barcia G, Beleza-Meireles A, Bernstein JA, Beygo J, Blanc P, Bramswig NC, Braun F, Buchzik D, Calame DG, Campbell J, Coutton C, Cunningham CA, Dargie N, Depienne C, Dipple KM, Dieux A, Dixit A, Dreyer L, Du H, El Chehadeh S, Field M, Ewans LJ, Geiger V, Gibbs RA, Glass I, Grunewald O, Gueguen P, Haack TB, Hadj Abdallah H, Harbuz R, Helbig I, Horvath J, Hustinx A, Isidor B, Jacquemont ML, Jamie F, Jeanne M, Kessler R, Klinkhammer H, Korenke GC, Kotzaeridou U, Krawitz P, Laurie S, Leventer RJ, Levy RJ, Lupski JR, Marijon P, McGinnis KE, Mendez R, Messaoud O, Nava C, Nizard M, O'Donnell-Luria A, O'Leary MC, Olivieri S, Parida A, Pehlivan D, Prentice AJ, Posey JE, Reuter CM, Satre V, Schluth-Bolard C, Smol T, Sultan T, Taylor J, Thauvin-Robinet C, Thevenon J, Uebergang E, Ueberberg S, Vincent-Delorme C, Wassmer E, Westwood E, Wheeler MT, Gulec EY, Vanderver A, Vossough A, Sanders SJ, Banka S, Findlay GM, MacArthur DG, Simons C, Whiffin N. Nat Genet. 2026 Apr;58(4):761-773. PMID: 41951959

De novo heterozygous variants of the RSF1 gene are responsible for a syndromic neurodevelopmental disorder
Jost C, Busa T, Wegner D, Shinawi M, Schaefer E, Piton A, Schluth-Bolard C, Charles P, Keren B, Mayerhanser K, Brunet T, Schatz U, Neil JE, Walsh CA, Sisco K, J Paul A; Undiagnosed Diseases Network; Lee C, Dykzeul N, Bonner D, Bernstein JA, Sutcliffe E, Wentzensen IM, Froehlich C, Liebler K, Galvin Parton P, Weiss-Burns J, Sagnol C, Delanne J, Racine C, Thauvin-Robinet C, Safraou H, Tran Mau-Them F, Duffourd Y, Bruel AL, Faivre L. Eur J Hum Genet. 2026 Apr;34(4):554-564. PMID: 41606215

Long-read genome sequencing and multi-omics in aging and neurodegeneration
Jensen TD, Le Guen Y, Talozzi L, Yang S, Gorzynski J, Peña-Tauber A, Stewart I, Ferrasse A, Nachun D, Arriaga MT, Lee J, Pulgrossi RC, Park J, Zhang J, Wagner AD, Mormino EC, Poston KL, Henderson VW, He Z, Wyss-Coray T, Montgomery SB, Ashley EA, Greicius MD. medRxiv [Preprint]. 2025 Oct 29:2025.10.10.25337775. PMID: 41282933

Transcriptome-wide outlier approach identifies individuals with minor spliceopathies
Arriaga TM, Mendez R, Ungar RA, Bonner DE, Matalon DR, Lemire G, Goddard PC, Padhi EM, Miller AM, Nguyen JV, Ma J, Smith KS, Scott SA, Liao L, Ng Z, Marwaha S, Bademci G, Bivona SA, Tekin M; Undiagnosed Diseases Network; Genomics Research to Elucidate the Genetics of Rare Diseases consortium; Bernstein JA, Montgomery SB, O'Donnell-Luria A, Wheeler MT, Ganesh VS. Am J Hum Genet. 2025 Oct 2;112(10):2458-2475. PMID: 40975062

Transcriptomic signatures of rare variant impacts across sex and the X chromosome
Ungar RA, Li T, Vetr NG, Ersaro N, Battle A, Montgomery SB. HGG Adv. 2025 Jul 10;6(3):100463. PMID: 40452186

Analytical validation of germline small variant detection using long-read HiFi genome sequencing
Hammond N, Liao L, Tong PW, Ng Z, Nguyen TP, Ho C, Yang Y, Scott SA. Genome Res. 2025 Jun 2;35(6):1391-1399. PMID: 40216554

Scaled multidimensional assays of variant effect identify sequence-function relationships in hypertrophic cardiomyopathy
Yamamoto Y, Chua K, Ferrasse A, Kirilova A, De Jong HN, Floyd BJ, Cadisch C, Wiel L, Wang Q, O'Neill MJ, Tabet D, Staudt D, Goryznski JE, Huang Y, Wilson RH, Sharma A, Tapales A, Agrawal R, Wheeler MT, MacRae C, Roden DM, Roth FP, Glazer AM, Ashley EA, Parikh VN. bioRxiv [Preprint]. 2025 May 27:2025.05.23.655878. PMID: 40501845

Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease
Jensen TD, Ni B, Reuter CM, Gorzynski JE, Fazal S, Bonner D, Ungar RA, Goddard PC, Raja A, Ashley EA, Bernstein JA, Zuchner S; Undiagnosed Diseases Network; Greicius MD, Montgomery SB, Schatz MC, Wheeler MT, Battle A. Genome Res. 2025 Apr 14;35(4):914-928. PMID: 40113264

Single cell variant to enhancer to gene map for coronary artery disease
Amrute JM, Lee PC, Eres I, Lee CJM, Bredemeyer A, Sheth MU, Yamawaki T, Gurung R, Anene-Nzelu C, Qiu WL, Kundu S, Li DY, Ramste M, Lu D, Tan A, Kang CJ, Wagoner RE, Alisio A, Cheng P, Zhao Q, Miller CL, Hall IM, Gupta RM, Hsu YH, Haldar SM, Lavine KJ, Jackson S, Andersson R, Engreitz JM, Foo RS, Li CM, Ason B, Quertermous T, Stitziel NO. medRxiv [Preprint]. 2024 Nov 13:2024.11.13.24317257. PMID: 39606421

Single-cell multi-omics map of human fetal blood in Down syndrome
Marderstein AR, De Zuani M, Moeller R, Bezney J, Padhi EM, Wong S, Coorens THH, Xie Y, Xue H, Montgomery SB, Cvejic A. Nature. 2024 Oct;634(8032):104-112. PMID: 39322663

Single-cell chromatin accessibility reveals malignant regulatory programs in primary human cancers
Sundaram L, Kumar A, Zatzman M, Salcedo A, Ravindra N, Shams S, Louie BH, Bagdatli ST, Myers MA, Sarmashghi S, Choi HY, Choi WY, Yost KE, Zhao Y, Granja JM, Hinoue T, Hayes DN, Cherniack A, Felau I, Choudhry H, Zenklusen JC, Farh KK, McPherson A, Curtis C, Laird PW; Cancer Genome Atlas Analysis Network‡; Demchok JA, Yang L, Tarnuzzer R, Caesar-Johnson SJ, Wang Z, Doane AS, Khurana E, Castro MAA, Lazar AJ, Broom BM, Weinstein JN, Akbani R, Kumar SV, Raphael BJ, Wong CK, Stuart JM, Safavi R, Benz CC, Johnson BK, Kyi C, Shen H, Corces MR, Chang HY, Greenleaf WJ. Science. 2024 Sep 6;385(6713):eadk9217. PMID: 39236169

RNA Sequencing in Disease Diagnosis
Smail C, Montgomery SB. Annu Rev Genomics Hum Genet. 2024 Aug;25(1):353-367. PMID: 38360541

Genome-Wide Genetic Associations Prioritize Evaluation of Causal Mechanisms of Atherosclerotic Disease Risk
Quertermous T, Li DY, Weldy CS, Ramste M, Sharma D, Monteiro JP, Gu W, Worssam MD, Palmisano BT, Park CY, Cheng P. Arterioscler Thromb Vasc Biol. 2024 Feb;44(2):323-327. PMID: 38266112

Impact of genome build on RNA-seq interpretation and diagnostics
Ungar RA, Goddard PC, Jensen TD, Degalez F, Smith KS, Jin CA; Undiagnosed Diseases Network; Bonner DE, Bernstein JA, Wheeler MT, Montgomery SB. Am J Hum Genet. 2024 Jul 11;111(7):1282-1300. PMID: 38834072

Integrated single-cell chromatin and transcriptomic analyses of human scalp identify gene-regulatory programs and critical cell types for hair and skin diseases
ber-Reynolds B, Wang C, Ko JM, Rios EJ, Aasi SZ, Davis MM, Oro AE, Greenleaf WJ. Nat Genet. 2023 Aug;55(8):1288-1300. PMID: 37500727

Organization of the human intestine at single-cell resolution
Hickey JW, Becker WR, Nevins SA, Horning A, Perez AE, Zhu C, Zhu B, Wei B, Chiu R, Chen DC, Cotter DL, Esplin ED, Weimer AK, Caraccio C, Venkataraaman V, Schürch CM, Black S, Brbić M, Cao K, Chen S, Zhang W, Monte E, Zhang NR, Ma Z, Leskovec J, Zhang Z, Lin S, Longacre T, Plevritis SK, Lin Y, Nolan GP, Greenleaf WJ, Snyder M. Nature. 2023 Jul;619(7970):572-584. PMID: 37468586

Deciphering the impact of genetic variation on human polyadenylation using APARENT2
Linder J, Koplik SE, Kundaje A, Seelig G. Genome Biol. 2022 Nov 5;23(1):232. PMID: 36335397

WhichTF is functionally important in your open chromatin data?
Tanigawa Y, Dyer ES, Bejerano G. PLoS Comput Biol. 2022 Aug 30;18(8):e1010378. PMID: 36040971

X-CAP improves pathogenicity prediction of stopgain variants
Ruchir Rastogi, Peter D Stenson, David N Cooper, Gill Bejerano. Genome Med. 2022 Jul 29;14(1):81. PMID: 35906703

NEAT-seq: simultaneous profiling of intra-nuclear proteins, chromatin accessibility and gene expression in single cells
Chen AF, Parks B, Kathiria AS, Ober-Reynolds B, Goronzy JJ, Greenleaf WJ. Nat Methods. 2022 May;19(5):547-553. PMID: 35501385

Toward transcriptomics as a primary tool for rare disease investigation
Stephen B Montgomery, Jonathan A Bernstein, Matthew T Wheeler. Cold Spring Harb Mol Case Stud. 2022 Mar 24;8(2):a006198. PMID: 35217565

Research from the Stanford Team

Combining Clinical and Polygenic Risk Improves Stroke Prediction Among Individuals With Atrial Fibrillation
O'Sullivan JW, Shcherbina A, Justesen JM, Turakhia M, Perez M, Wand H, Tcheandjieu C, Clarke SL, Rivas MA, Ashley EA. Circ Genom Precis Med. 2021 Jun;14(3):e003168. PMID: 34029116

A genome-wide atlas of co-essential modules assigns function to uncharacterized genes
Wainberg M, Kamber RA, Balsubramani A, Meyers RM, Sinnott-Armstrong N, Hornburg D, Jiang L, Chan J, Jian R, Gu M, Shcherbina A, Dubreuil MM, Spees K, Meuleman W, Snyder MP, Bassik MC, Kundaje A. Nat Genet. 2021 May;53(5):638-649. PMID: 33859415

Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics
Bonder MJ, Smail C, Gloudemans MJ, Frésard L, Jakubosky D, D'Antonio M, Li X, Ferraro NM, Carcamo-Orive I, Mirauta B, Seaton DD, Cai N, Vakili D, Horta D, Zhao C, Zastrow DB, Bonner DE; HipSci Consortium; iPSCORE consortium; Undiagnosed Diseases Network; PhLiPS consortium, Wheeler MT, Kilpinen H, Knowles JW, Smith EN, Frazer KA, Montgomery SB, Stegle O. Nat Genet. 2021 Mar;53(3):313-321. PMID: 33664507

Functional and structural analysis of cytokine-selective IL6ST defects that cause recessive hyper-IgE syndrome
Chen YH, Zastrow DB, Metcalfe RD, Gartner L, Krause F, Morton CJ, Marwaha S, Fresard L, Huang Y, Zhao C, McCormack C, Bick D, Worthey EA, Eng CM, Gold J; Undiagnosed Diseases Network, Montgomery SB, Fisher PG, Ashley EA, Wheeler MT, Parker MW, Shanmugasundaram V, Putoczki TL, Schmidt-Arras D, Laurence A, Bernstein JA, Griffin MDW, Uhlig HH. J Allergy Clin Immunol. 2021 Mar 23:S0091-6749(21)00471-1. PMID: 33771552

AMELIE speeds Mendelian diagnosis by matching patient phenotype and genotype to primary literature
Birgmeier J, Haeussler M, Deisseroth CA, Steinberg EH, Jagadeesh KA, Ratner AJ, Guturu H, Wenger AM, Diekhans ME, Stenson PD, Cooper DN, Ré C, Beggs AH, Bernstein JA, Bejerano G. Sci Transl Med. 2020 May 20;12(544):eaau9113. PMID: 32434849

AVADA: Towards Automated Pathogenic Variant Evidence Retrieval Directly from the Full Text Literature
Birgmeier J, Deisseroth CA, Hayward LE, Galhardo LMT, Tierno AP, Jagadeesh KA, Stenson PD, Cooper DN, Bernstein JA, Haeussler M, Bejerano G. Genet Med. 2020 Feb;22(2):362-370. PMID: 31467448

ClinPhen extracts and prioritizes patient phenotypes directly from medical records to expedite genetic disease diagnosis
Deisseroth CA, Birgmeier J, Bodle EE, Kohler JN, Matalon DR, Nazarenko Y, Genetti CA, Brownstein CA, Schmitz-Abe K, Schoch K, Cope H, Signer R; Undiagnosed Diseases Network, Martinez-Agosto JA, Shashi V, Beggs AH, Wheeler MT, Bernstein JA, Bejerano G. Genet Med. 2019 Jul;21(7):1585-1593. PMID: 30514889

Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
Frésard L, Smail C, Ferraro NM, Teran NA, Li X, Smith KS, Bonner D, Kernohan KD, Marwaha S, Zappala Z, Balliu B, Davis JR, Liu B, Prybol CJ, Kohler JN, Zastrow DB, Reuter CM, Fisk DG, Grove ME, Davidson JM, Hartley T, Joshi R, Strober BJ, Utiramerur S; Undiagnosed Diseases Network; CareRare Canada Consortium, Lind L, Ingelsson E, Battle A, Bejerano G, Bernstein JA, Ashley EA, Boycott KM, Merker JD, Wheeler MT, Montgomery SB. Nat Med.2019 Jun;25(6):911-919. PMID: 31160820

S-CAP extends pathogenicity prediction to genetic variants that affect RNA splicing
Jagadeesh KA, Paggi JM, Ye JS, Stenson PD, Cooper DN, Bernstein JA, Bejerano G. Nat Genet. 2019 Apr;51(4):755-763. PMID: 30804562

Phrank measures phenotype sets similarity to greatly improve Mendelian diagnostic disease prioritization
Jagadeesh KA, Birgmeier J, Guturu H, Deisseroth CA, Wenger AM, Bernstein JA, Bejerano G. Genet Med. 2019 Feb;21(2):464-470. PMID: 29997393

Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease
Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, Eng CM, Esteves C, Gahl WA, Hamid R, Jacob HJ, Kikani B, Koeller DM, Kohane IS, Lee BH, Loscalzo J, Luo X, McCray AT, Metz TO, Mulvihill JJ, Nelson SF, Palmer CGS, Phillips JA 3rd, Pick L, Postlethwait JH, Reuter C, Shashi V, Sweetser DA, Tifft CJ, Walley NM, Wangler MF, Westerfield M, Wheeler MT, Wise AL, Worthey EA, Yamamoto S, Ashley EA; Undiagnosed Diseases Network. N Engl J Med.2018 Nov 29;379(22):2131-2139. PMID: 30304647

Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder
Monika Oláhová, Wan Hee Yoon, Kyle Thompson, Sharayu Jangam, Liliana Fernandez, Jean M. Davidson, Jennifer E. Kyle, Megan E. Grove, Dianna G. Fisk, Jennefer N. Kohler, Matthew Holmes, Annika M. Dries, Yong Huang, Chunli Zhao, Kévin Contrepois, Zachary Zappala, Laure Frésard, Daryl Waggott, Erika M. Zink, Young-Mo Kim, Heino M. Heyman, Kelly G. Stratton, Bobbie-Jo M. Webb-Robertson, Undiagnosed Diseases Network, Michael Snyder, Jason D. Merker, Stephen B. Montgomery, Paul G. Fisher, René G. Feichtinger, Johannes A. Mayr, Julie Hall, Ines A. Barbosa, Michael A. Simpson, Charu Deshpande, Katrina M. Waters, David M. Koeller, Thomas O. Metz, Andrew A. Morris, Susan Schelley, Tina Cowan, Marisa W. Friederich, Robert McFarland, Johan L.K. Van Hove, Gregory M. Enns, Shinya Yamamoto, Euan A. Ashley, Michael F. Wangler, Robert W. Taylor, Hugo J. Bellen, Jonathan A. Bernstein, and Matthew T. Wheeler. Am J Hum Genet. 2018 Mar 1; 102(3): 494–504. PMID: 29478781

Long-read genome sequencing identifies causal structural variation in a Mendelian disease Running title: Long-read WGS identifies causal SV in a Mendelian disease
Merker JD, Wenger AM, Sneddon T, Grove M, Zappala Z, Fresard L, Waggott D, Utiramerur S, Hou Y, Smith KS, Montgomery SB, Wheeler M, Buchan JG, Lambert CC, Eng KS, Hickey L, Korlach J, Ford J, Ashley EA. Genet Med. 2018 Jan;20(1): 159-163. PMID: 28640241

Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers
Wenger AM, Guturu H, Bernstein JA, Bejerano G. Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers. Genet Med. 2017 Feb;19(2):209-214. PMID: 27441994

M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity
Jagadeesh KA, Wenger AM, Berger MJ, Guturu H, Stenson PD, Cooper DN, Bernstein JA, Bejerano G. Nat Genet. 2016 Dec;48(12):1581-1586. PMID: 27776117