Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases DOI Creative Commons
Maja Thiele, Ida Falk Villesen, Lili Niu

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(2), P. 345 - 359

Published: March 28, 2024

The rising prevalence of liver diseases related to obesity and excessive use alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis steatohepatitis significant fibrosis, monitoring, prognostication prediction treatment efficacy. Breakthroughs in omics methodologies the power bioinformatics have created excellent opportunity apply technological advances clinical needs, instance development precision personalised medicine. Via technologies, biological processes from genes circulating protein, as well microbiome - including bacteria, viruses fungi, can be investigated on axis. However, there are important barriers omics-based biomarker discovery validation, semi-quantitative measurements untargeted platforms, which may exhibit high analytical, inter- intra-individual variance. Standardising methods need validate them across diverse populations presents a challenge, partly due disease complexity dynamic nature expression different stages. Lack validity causes lost opportunities when studies fail provide knowledge needed regulatory approvals, all contributes delayed translation these discoveries into practice. While no matured implementation, extent data generated has enabled hypothesis-free plethora candidate that warrant further validation. To explore many hepatologists detailed commonalities differences between various layers, both advantages approaches.

Language: Английский

Multimodal biomedical AI DOI Open Access
Julián Acosta, Guido J. Falcone, Pranav Rajpurkar

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(9), P. 1773 - 1784

Published: Sept. 1, 2022

Language: Английский

Citations

572
Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains DOI
Ditte Demontis, G. Bragi Walters, Georgios Athanasiadis

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(2), P. 198 - 208

Published: Jan. 26, 2023

Language: Английский

Citations

374
Bringing the Animal QTLdb and CorrDB into the future: meeting new challenges and providing updated services DOI Creative Commons

Zhi-Liang Hu,

Carissa A. Park,

James M. Reecy

et al.

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 50(D1), P. D956 - D961

Published: Oct. 22, 2021

Abstract The Animal QTLdb (https://www.animalgenome.org/QTLdb) and CorrDB (https://www.animalgenome.org/CorrDB) are unique resources for livestock animal genetics genomics research which have been used extensively by the international genome community. This is largely due to active development of databases over years keep up with rapid advancement sciences. ongoing has ensured that these provide researchers not only continually updated data but also new web tools disseminate data. Through our continued efforts, evolved from original Pig cross-experiment QTL comparisons an hosting 220 401 QTL, SNP association eQTL linking phenotype genotype 2210 traits. In addition, there 23 552 correlations 866 traits 4273 heritability on 1069 in CorrDB. All were curated 3157 publications cover seven species. Along curation, species, additional builds, functions features built into as well. Standardized procedures support mapping multiple species/genome builds ability browse based linked ontology terms highlights recent developments.

Language: Английский

Citations

241
The complex genetic architecture of Alzheimer's disease: novel insights and future directions DOI Creative Commons
Shea J. Andrews, Alan E. Renton, Brian Fulton‐Howard

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 90, P. 104511 - 104511

Published: March 10, 2023

Language: Английский

Citations

187
Applications of multi‐omics analysis in human diseases DOI Creative Commons

Chongyang Chen,

Jing Wang,

Donghui Pan

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: July 31, 2023

Multi-omics usually refers to the crossover application of multiple high-throughput screening technologies represented by genomics, transcriptomics, single-cell proteomics and metabolomics, spatial so on, which play a great role in promoting study human diseases. Most current reviews focus on describing development multi-omics technologies, data integration, particular disease; however, few them provide comprehensive systematic introduction multi-omics. This review outlines existing technical categories multi-omics, cautions for experimental design, focuses integrated analysis methods especially approach machine learning deep integration corresponding tools, medical researches (e.g., cancer, neurodegenerative diseases, aging, drug target discovery) as well open-source tools databases, finally, discusses challenges future directions precision medicine. With algorithms, important disease research, also provided detailed introduction. will guidance researchers, who are just entering into research.

Language: Английский

Citations

172
Large-scale plasma proteomics comparisons through genetics and disease associations DOI Creative Commons
Grímur Hjörleifsson Eldjárn, Egil Ferkingstad, Sigrún H. Lund

et al.

Nature, Journal Year: 2023, Volume and Issue: 622(7982), P. 348 - 358

Published: Oct. 4, 2023

High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge gap between genome diseases. Here we performed association studies Olink Explore 3072 data generated by UK Biobank Pharma Proteomics Project

Language: Английский

Citations

167
New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications DOI Open Access
Ole A. Andreassen, Guy Hindley, Oleksandr Frei

et al.

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(1), P. 4 - 24

Published: Jan. 14, 2023

Psychiatric genetics has made substantial progress in the last decade, providing new insights into genetic etiology of psychiatric disorders, and paving way for precision psychiatry, which individual profiles may be used to personalize risk assessment inform clinical decision‐making. Long recognized heritable, recent evidence shows that disorders are influenced by thousands variants acting together. Most these commonly occurring, meaning every a each disorder, from low high. A series large‐scale studies have discovered an increasing number common rare robustly associated with major disorders. The most convincing biological interpretation findings implicates altered synaptic function autism spectrum disorder schizophrenia. However, mechanistic understanding is still incomplete. In line their extensive epidemiological overlap, appear exist on continua share large degree one another. This provides further support notion current diagnoses do not represent distinct pathogenic entities, ongoing attempts reconceptualize nosology. also influences range behavioral somatic traits diseases, including brain structures, cognitive function, immunological phenotypes cardiovascular disease, suggesting shared potential importance. Current polygenic score tools, predict susceptibility illness, yet provide clinically actionable information. likely improve coming years, they eventually become part practice, stressing need educate clinicians patients about use misuse. review discusses key possible applications, suggests future directions.

Language: Английский

Citations

132
Physiological and pathological roles of lipogenesis DOI
Yong Geun Jeon, Ye Young Kim, Gung Lee

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(5), P. 735 - 759

Published: May 4, 2023

Language: Английский

Citations

109
Challenges and Opportunities for Developing More Generalizable Polygenic Risk Scores DOI
Ying Wang, Kristin Tsuo, Masahiro Kanai

et al.

Annual Review of Biomedical Data Science, Journal Year: 2022, Volume and Issue: 5(1), P. 293 - 320

Published: May 16, 2022

Polygenic risk scores (PRS) estimate an individual's genetic likelihood of complex traits and diseases by aggregating information across multiple variants identified from genome-wide association studies. PRS can predict a broad spectrum have therefore been widely used in research settings. Some work has investigated their potential applications as biomarkers preventative medicine, but significant is still needed to definitively establish communicate absolute patients for modifiable factors demographic groups. However, the biggest limitation currently that they show poor generalizability diverse ancestries cohorts. Major efforts are underway through methodological development data generation initiatives improve generalizability. This review aims comprehensively discuss current progress on PRS, affect generalizability, promising areas improving accuracy, portability, implementation.

Language: Английский

Citations

101
Leveraging base-pair mammalian constraint to understand genetic variation and human disease DOI
Patrick F. Sullivan, Jennifer R. S. Meadows, Steven Gazal

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6643)

Published: April 27, 2023

Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability discern which positions functionally important. Evolutionary constraint is a powerful predictor function, agnostic cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% the genome as significantly constrained and likely functional. We compared annotation, association studies, copy-number variation, clinical genetics findings, cancer data. Constrained enriched for variants that explain common heritability more than other functional annotations. Our results improve variant annotation also highlight regulatory landscape still needs be further explored linked disease.

Language: Английский

Citations

69