Candidate Denisovan fossils identified through gene regulatory phenotyping DOI Open Access

Nadav Mishol,

Gadi Herzlinger,

Yoel Rak

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 18, 2024

Abstract Denisovans are an extinct group of humans whose morphology is mostly unknown. The scarcity verified Denisovan fossils makes it challenging to study their anatomy, and how well they were adapted environment. We previously developed a genetic phenotyping approach gain insight into anatomy by detecting gene regulatory changes that likely altered skeletal morphology. Here, we scan Middle Pleistocene crania for unclassified or disputed specimens match predicted thus might be related Denisovans. found Harbin , Dali Kabwe 1 show particularly good alignment with the profile, most phenotypes matching anatomy. conclude our could help classify unidentified specimens, exhibit Denisovan-like closely linked lineage.

Language: Английский

A Litmus Test for Confounding in Polygenic Scores DOI Creative Commons
Samuel Pattillo Smith, Olivia S. Smith, Hakhamanesh Mostafavi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Polygenic scores (PGSs) are being rapidly adopted for trait prediction in the clinic and beyond. PGSs often thought of as capturing direct genetic effect one’s genotype on their phenotype. However, because constructed from population-level associations, they influenced by factors other than effects, including stratification, assortative mating, dynastic effects (“SAD effects”). Our interpretation application may hinge relative impact SAD since be environmentally or culturally mediated. We developed a method that estimates proportion variance PGS (in given sample) is driven covariance. leverage comparison interest based standard GWAS with sibling GWAS—which largely immune to effects—to quantify contribution each type interest. method, Partitioning Genetic Scores Using Siblings (PGSUS, pron. “Pegasus”), breaks down components further axes ancestry, allowing nuanced effects. In particular, PGSUS can detect stratification along major ancestry well “isotropic” respect ancestry. Applying PGSUS, we found evidence using large meta-analyses height educational attainment range UK Biobank. some instances, appears stratified axis one sample but not another (for example, comparisons samples different countries, ancient DNA vs. contemporary samples). Finally, show approaches adjustment population structure GWASs have distinct advantages mitigation ancestry-axis-specific isotropic PGS. study illustrates how family-based designs combined population-based guide genomic predictors.

Language: Английский

Citations

1
Advancements in Gene Structure Prediction: Innovation and Prospects of Deep Learning Models Apply in Multi-species DOI Creative Commons
Tong Wang, H. J. Yang,

Ting Xu

et al.

Published: Jan. 25, 2025

In recent years, advancements in gene structure prediction have been significantly driven by the integration of deep learning technologies into bioinformatics. Transitioning from traditional thermodynamics and comparative genomics methods to modern learning-based models such as CDSBERT, DNABERT, RNA-FM, PlantRNA-FM accuracy generalization seen remarkable improvements. These models, leveraging genome sequence data along with secondary tertiary information, facilitated diverse applications studying functions across animals, plants, humans. They also hold substantial potential for multi-application early disease diagnosis, personalized treatment, genomic evolution research. This review combines learning, showcasing functional region annotation, protein-RNA interactions, cross-species analysis. It highlights their contributions animal, plant, human research while exploring future opportunities cancer mutation prediction, RNA vaccine design, CRISPR editing optimization. The emphasizes directions, model refinement, multimodal integration, global collaboration. By offering a concise overview forward-looking insights, this article aims provide foundational resource practical guidance advancing nucleic acid

Language: Английский

Citations

0
Inferring human phenotypes using ancient DNA: from molecules to populations DOI
Manuel Ferrando-Bernal, Colin M. Brand, John A. Capra

et al.

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 90, P. 102283 - 102283

Published: Nov. 29, 2024

Language: Английский

Citations

3
Candidate Denisovan fossils identified through gene regulatory phenotyping DOI Open Access

Nadav Mishol,

Gadi Herzlinger,

Yoel Rak

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 18, 2024

Abstract Denisovans are an extinct group of humans whose morphology is mostly unknown. The scarcity verified Denisovan fossils makes it challenging to study their anatomy, and how well they were adapted environment. We previously developed a genetic phenotyping approach gain insight into anatomy by detecting gene regulatory changes that likely altered skeletal morphology. Here, we scan Middle Pleistocene crania for unclassified or disputed specimens match predicted thus might be related Denisovans. found Harbin , Dali Kabwe 1 show particularly good alignment with the profile, most phenotypes matching anatomy. conclude our could help classify unidentified specimens, exhibit Denisovan-like closely linked lineage.

Language: Английский

Citations

1