Polymorphism of SERF2, the gene encoding a heat-resistant obscure (Hero) protein with chaperone activity, is a novel link in ischemic stroke DOI Creative Commons
А. Е. Белых, Vladislav O. Soldatov,

T. A. Stetskaya

et al.

IBRO Neuroscience Reports, Journal Year: 2023, Volume and Issue: 14, P. 453 - 461

Published: May 10, 2023

Ischemic stroke (IS) is one of the most serious cardiovascular events associated with high risk death or disability. The growing body evidence highlights molecular chaperones as especially important players in pathogenesis disease. Since six small proteins called "Hero" have been recently identified a novel class we aimed to evaluate whether SNP rs4644832

Language: Английский

Annotating and prioritizing human non-coding variants with RegulomeDB v.2 DOI Open Access
Shengcheng Dong, Nanxiang Zhao,

Emma Spragins

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(5), P. 724 - 726

Published: April 25, 2023

Language: Английский

Citations

88
CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods DOI Creative Commons
Shantanu Jain, Constantina Bakolitsa, Steven E. Brenner

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Feb. 22, 2024

Abstract Background The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction genetic variant impact, particularly where relevant disease. five complete editions CAGI community experiment comprised 50 challenges, in which participants made blind predictions phenotypes from data, and these were evaluated by independent assessors. Results Performance was strong clinical pathogenic variants, including some difficult-to-diagnose cases, extends interpretation cancer-related variants. Missense methods able estimate biochemical effects with increasing accuracy. regulatory variants complex trait disease risk less definitive indicates performance potentially suitable auxiliary use clinic. Conclusions show that while current are imperfect, they have major utility research applications. Emerging increasingly large, robust datasets training assessment promise further progress ahead.

Language: Английский

Citations

38
The landscape of host genetic factors involved in immune response to common viral infections DOI Creative Commons
Linda Kachuri, Stephen Francis, Maike L. Morrison

et al.

Genome Medicine, Journal Year: 2020, Volume and Issue: 12(1)

Published: Oct. 27, 2020

Abstract Background Humans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the mechanisms of immune response to viral infection provides insight into disease etiology therapeutic opportunities. Methods We conducted comprehensive study including genome-wide transcriptome-wide association analyses identify loci associated with immunoglobulin G antibody 28 antigens 16 using serological data from 7924 European ancestry participants UK Biobank cohort. Results Signals human leukocyte antigen (HLA) class II region dominated landscape response, 40 independent 14 classical alleles, 7 which exhibited pleiotropic effects across families. identified specific amino acid (AA) residues that are seroreactivity, strongest associations presented range AA positions within DRβ1 at 11, 13, 71, 74 Epstein-Barr virus (EBV), Varicella zoster (VZV), herpesvirus 7, (HHV7), Merkel cell polyomavirus (MCV). Genome-wide discovered novel outside HLA ( P < 5.0 × 10 −8 ), FUT2 (19q13.33) BK (BKV), STING1 (5q31.2) MCV, CXCR5 (11q23.3) TBKBP1 (17q21.32) HHV7. Transcriptome-wide 114 genes infection, 12 region, ECSCR : = −15 (MCV), NTN5 1.1 −9 P2RY13 EBV nuclear antigen. also demonstrated pleiotropy between diseases, autoimmune disorders cancer neurodegenerative psychiatric conditions. Conclusions Our confirms importance elucidates determinants beyond contribute host-virus interaction.

Language: Английский

Citations

98
Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells DOI Creative Commons
Bhuwan Khatri, Kandice L. Tessneer, Astrid Rasmussen

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 27, 2022

Abstract Sjögren’s disease is a complex autoimmune with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel significant (GWS) regions in cases of European ancestry: CD247 , NAB1 PTTG1-MIR146A PRDM1-ATG5 TNFAIP3 XKR6 MAPT- CRHR1 RPTOR-CHMP6-BAIAP6 TYK2 SYNGR1 . Polygenic risk scores yield predictability (AUROC = 0.71) and relative 12.08. Interrogation bioinformatics databases refine the associations, define local regulatory networks GWS SNPs from 95% credible set, expand implicated gene list to >40. Many are eQTLs for genes within topologically associated domains immune cells and/or main target tissue, salivary glands.

Language: Английский

Citations

63
Systematic investigation of allelic regulatory activity of schizophrenia-associated common variants DOI Creative Commons
Jessica C. McAfee, Sool Lee, Jiseok Lee

et al.

Cell Genomics, Journal Year: 2023, Volume and Issue: 3(10), P. 100404 - 100404

Published: Sept. 15, 2023

Genome-wide association studies (GWASs) have successfully identified 145 genomic regions that contribute to schizophrenia risk, but linkage disequilibrium makes it challenging discern causal variants. We performed a massively parallel reporter assay (MPRA) on 5,173 fine-mapped GWAS variants in primary human neural progenitors and 439 with allelic regulatory effects (MPRA-positive variants). Transcription factor binding had modest predictive power, while fine-map posterior probability, enhancer overlap, evolutionary conservation failed predict MPRA-positive Furthermore, 64% of did not exhibit expressive quantitative trait loci signature, suggesting MPRA could identify yet unexplored potentials. To the combinatorial effect gene regulation, we propose an accessibility-by-contact model combines MPRA-measured activity neuronal chromatin architecture.

Language: Английский

Citations

24
Artificial intelligence-driven biomedical genomics DOI Open Access
Kairui Guo, Mengjia Wu,

Zelia Soo

et al.

Knowledge-Based Systems, Journal Year: 2023, Volume and Issue: 279, P. 110937 - 110937

Published: Sept. 7, 2023

Language: Английский

Citations

23
Decoding Non-coding Variants: Recent Approaches to Studying Their Role in Gene Regulation and Human Diseases DOI Creative Commons
Edwin G. Peña-Martínez, José A. Rodríguez‐Martínez

Frontiers in Bioscience-Scholar, Journal Year: 2024, Volume and Issue: 16(1)

Published: March 1, 2024

Genome-wide association studies (GWAS) have mapped over 90% of disease- and quantitative-trait-associated variants within the non-coding genome. Non-coding regulatory DNA (e.g., promoters enhancers) RNA 5′ 3′ UTRs splice sites) are essential in regulating temporal tissue-specific gene expressions. can potentially impact phenotype an organism by altering molecular recognition cis-regulatory elements, leading to dysregulation. However, determining causality between variants, regulation, human disease has remained challenging. Experimental computational methods been developed understand mechanism involved variant interference at transcriptional post-transcriptional levels. This review discusses recent approaches evaluating disease-associated single-nucleotide (SNVs) determines their on transcription factor (TF) binding, expression, chromatin conformation, translation.

Language: Английский

Citations

13
Reports from the fifth edition of CAGI: The Critical Assessment of Genome Interpretation DOI
Gaia Andreoletti,

Lipika R. Pal,

John Moult

et al.

Human Mutation, Journal Year: 2019, Volume and Issue: 40(9), P. 1197 - 1201

Published: July 23, 2019

Interpretation of genomic variation plays an essential role in the analysis cancer and monogenic disease, increasingly also complex trait with applications ranging from basic research to clinical decisions. Many computational impact prediction methods have been developed, yet field lacks a clear consensus on their appropriate use interpretation. The Critical Assessment Genome (CAGI, /'kā-jē/) is community experiment objectively assess for predicting phenotypic impacts variation. CAGI participants are provided genetic variants make blind predictions resulting phenotype. Independent assessors evaluate by comparing experimental data. has completed five editions goals establishing state art genome interpretation encouraging new methodological developments. This special issue (https://onlinelibrary.wiley.com/toc/10981004/2019/40/9) comprises reports CAGI, focusing fifth edition that culminated conference took place 5 7 July 2018. CAGI5 was comprised 14 challenges engaged hundreds dozen countries. had notable increase splicing expression regulatory variant challenges, while continuing genomics, as well disease datasets missense diseases Pompe schizophrenia. Full information about at https://genomeinterpretation.org.

Language: Английский

Citations

58
Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia DOI Creative Commons
Linda Kachuri, Soyoung Jeon, Andrew T. DeWan

et al.

The American Journal of Human Genetics, Journal Year: 2021, Volume and Issue: 108(10), P. 1823 - 1835

Published: Aug. 31, 2021

Language: Английский

Citations

50
Dissecting the genetic overlap between severe mental disorders and markers of cellular aging: Identification of pleiotropic genes and druggable targets DOI
Claudia Pisanu,

Donatella Congiu,

Anna Maria Meloni

et al.

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(6), P. 1033 - 1041

Published: Feb. 24, 2024

Language: Английский

Citations

7