GenePy identifies potential missed biallelic diagnoses in the 100KGP by scoring variants and analyzing phenotypic overlaps, finding 14% of undiagnosed participants may have a missed diagnosis.

Genetics in Medicine · Jan 18, 2024Peer-reviewedGenetic & Genomic Medicine

Mutation-Attention (MuAt): deep representation learning of somatic mutations for tumour typing and subtyping

Prima Sanjaya, Katri Maljanen, Riku Katainen, Sebastian M. Waszak, John C. Ambrose, P. Arumugam, Roel P. J. Bevers, Marta Bleda, F. Boardman-Pretty, Christopher R. Boustred, Helen K. Brittain, Matthew Arthur Brown, Mark J. Caulfield, G. C. Chan, Adam P Giess, , Esa Pitkänen

The paper introduces MuAt, a deep learning model that learns representations of somatic mutations to predict tumour types and subtypes with high accuracy.

Genome Medicine · Jul 7, 2023Peer-reviewedGenomics

Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration

Annalisa Vetro, Cristiana Pelorosso, Simona Balestrini, Alessio Masi, Sophie Hambleton, Emanuela Argilli, Valerio Conti, Simone Giubbolini, Rebekah Barrick, Gaber Bergant, Karin Writzl, Emilia K. Bijlsma, Theresa Brunet, Pilar Cacheiro, Davide Mei, , Ellen Thomas

This study identifies TMEM63B variants in patients with developmental and epileptic encephalopathy and neurodegeneration, showing altered cation currents and hematological abnormalities.

The American Journal of Human Genetics · Jul 7, 2023Peer-reviewedGenetic & Genomic Medicine

Targeting de novo loss of function variants in constrained disease genes improves diagnostic rates in the 100,000 Genomes Project

Eleanor G. Seaby, Neil Thomas, Amy Webb, Helen K. Brittain, Ana Lisa Taylor Tavares, John C. Ambrose, Prabhu Arumugam, Roel P. J. Bevers, Marta Bleda, F Boardman-Pretty, Christopher R. Boustred, Mark J. Caulfield, G. C. Chan, Tom Fowler, Adam P Giess, , Sarah Ennis

The paper introduces DeNovoLOEUF, a method to identify diagnostic variants in genome sequencing data, achieving 96% positive predictive value and uncovering 39 missed diagnoses in the 100,000 Genomes Project.

Human Genetics · Dec 7, 2022Peer-reviewedGenetic & Genomic Medicine

Mendelian gene identification through mouse embryo viability screening

Pilar Cacheiro, Carl Henrik Westerberg, Jesse Mager, Mary E. Dickinson, Lauryl M. J. Nutter, Violeta Muñoz‐Fuentes, Chih‐Wei Hsu, Ignatia B. Van den Veyver, Ann Marie Flenniken, Colin McKerlie, Stephen A. Murray, Lydia Teboul, Jason D. Heaney, K. C. Kent Lloyd, Louise Lanoue, , John Pullinger

The paper identifies novel Mendelian genes by analyzing mouse embryo lethality and linking them to human disease phenotypes and genetic variants.

Genome Medicine · Oct 13, 2022Peer-reviewedGenetic & Genomic Medicine

An intermediate effect size variant in UMOD confers risk for chronic kidney disease

Eric Gregory Olinger, Céline Schaeffer, Kendrah O. Kidd, Elhussein A. E. Elhassan, Yurong Cheng, Inès Dufour, Guglielmo Schiano, Holly R. Mabillard, Elena Pasqualetto, Patrick Hofmann, Daniel Guido Fuster, Andreas David Kistler, Ian Wilson, Stanislav Kmoch, Laure Raymond, , Magdalena Zarowiecki

The paper identifies an intermediate-effect variant in UMOD associated with chronic kidney disease risk and shows it has reduced disease severity compared to canonical ADTKD mutations.

Proceedings of the National Academy of Sciences · Aug 10, 2022Peer-reviewedGenetic & Genomic Medicine

Dissecting the eQTL micro-architecture in Caenorhabditis elegans

Mark G. Sterken, Roel P. J. Bevers, Rita J. M. Volkers, Joost A. G. Riksen, Jan E. Kammenga, Basten L. Snoek

This study maps eQTL in C. elegans RILs across environments, showing higher reproducibility of local eQTL and environmental effects on eQTL micro-architecture.

Frontiers in Genetics · Nov 3, 2020Peer-reviewedGenetics

Extensive mitochondrial population structure and haplotype-specific phenotypic variation in the Drosophila Genetic Reference Panel

Roel P. J. Bevers, Maria Litovchenko, Adamandia Kapopoulou, Virginie S. Braman, Matthew R. Robinson, Johan H. Auwerx, Brian Hollis, Bart Deplancke

The paper analyzes mitochondrial variation in the DGRP, identifies haplotype-specific phenotypic associations, and finds no major fitness effects from mito-nuclear incompatibilities.

bioRxiv · Nov 9, 2018 · PreprintGenomics

Temporal dynamics of gene expression in heat-stressed Caenorhabditis elegans

Katharina Jovic, Mark G. Sterken, Jacopo Grilli, Roel P. J. Bevers, Miriam García Rodríguez, Joost A. G. Riksen, Stefano Allesina A, Jan E. Kammenga, Basten L. Snoek

This study examines gene expression changes in C. elegans during heat stress, identifying a critical time window where gene expression shifts and phenotypic damage becomes irreversible.

PLoS ONE · Dec 11, 2017Peer-reviewedGenomics

Contribution of trans regulatory eQTL to cryptic genetic variation in C. elegans

Basten L. Snoek, Mark G. Sterken, Roel P. J. Bevers, Rita J. M. Volkers, Arjèn E. van’t Hof, Rachel Brenchley, Joost A. G. Riksen, Andrew R. Cossins, Jan E. Kammenga

The paper investigates how trans regulatory eQTL contribute to cryptic genetic variation in C. elegans under heat stress and recovery conditions.

BMC Genomics · Jun 29, 2017Peer-reviewedGenetics