A guide for the diagnosis of rare and undiagnosed disease: beyond the exome
Rare diseases affect 30 million people in the USA and more than 300–400 million
worldwide, often causing chronic illness, disability, and premature death. Traditional …
worldwide, often causing chronic illness, disability, and premature death. Traditional …
The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting
PD Stenson, M Mort, EV Ball, M Chapman, K Evans… - Human genetics, 2020 - Springer
Abstract The Human Gene Mutation Database (HGMD®) constitutes a comprehensive
collection of published germline mutations in nuclear genes that are thought to underlie, or …
collection of published germline mutations in nuclear genes that are thought to underlie, or …
Accurate proteome-wide missense variant effect prediction with AlphaMissense
The vast majority of missense variants observed in the human genome are of unknown
clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on …
clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on …
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Schizophrenia has a heritability of 60–80%, much of which is attributable to common risk
alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with …
alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with …
Rare coding variants in ten genes confer substantial risk for schizophrenia
Rare coding variation has historically provided the most direct connections between gene
function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 …
function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 …
Transfer learning enables predictions in network biology
Mapping gene networks requires large amounts of transcriptomic data to learn the
connections between genes, which impedes discoveries in settings with limited data …
connections between genes, which impedes discoveries in settings with limited data …
Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes
To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of
rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new …
rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new …
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
Trait-associated genetic variants affect complex phenotypes primarily via regulatory
mechanisms on the transcriptome. To investigate the genetics of gene expression, we …
mechanisms on the transcriptome. To investigate the genetics of gene expression, we …
A clinically applicable integrative molecular classification of meningiomas
Meningiomas are the most common primary intracranial tumour in adults. Patients with
symptoms are generally treated with surgery as there are no effective medical therapies. The …
symptoms are generally treated with surgery as there are no effective medical therapies. The …
CADD-Splice—improving genome-wide variant effect prediction using deep learning-derived splice scores
Background Splicing of genomic exons into mRNAs is a critical prerequisite for the accurate
synthesis of human proteins. Genetic variants impacting splicing underlie a substantial …
synthesis of human proteins. Genetic variants impacting splicing underlie a substantial …