A5039958070- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- RNA Research and Splicing
- Genetic factors in colorectal cancer
- Genomics and Phylogenetic Studies
- Cancer Genomics and Diagnostics
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Genetic Associations and Epidemiology
- Genomic variations and chromosomal abnormalities
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Biomedical Text Mining and Ontologies
- Multiple and Secondary Primary Cancers
- Genetic Neurodegenerative Diseases
- Forensic and Genetic Research
- Neurofibromatosis and Schwannoma Cases
- Protein Structure and Dynamics
- Machine Learning in Bioinformatics
- Mitochondrial Function and Pathology
- Gastric Cancer Management and Outcomes
- Ubiquitin and proteasome pathways
Cardiff University
2015-2025
University Hospital of Wales
2023
Griffith University
2015-2019
Laboratory of Excellence GR-Ex
2018
Washington Center
2018
University of Washington
2018
RELX Group (Netherlands)
2018
Indiana University School of Medicine
2012-2015
Indiana University – Purdue University Indianapolis
2008-2015
Data61
2015
The Human Gene Mutation Database (HGMD) constitutes a comprehensive core collection of data on germ-line mutations in nuclear genes underlying or associated with human inherited disease (www.hgmd.org). Data catalogued includes: single base-pair substitutions coding, regulatory and splicing-relevant regions; micro-deletions micro-insertions; indels; triplet repeat expansions as well gross deletions; insertions; duplications; complex rearrangements. Each mutation is entered into HGMD only once...
Abstract The Human Gene Mutation Database (HGMD ® ) is a comprehensive core collection of germline mutations in nuclear genes that underlie or are associated with human inherited disease. Here, we summarize the history database and its current resources. By December 2008, contained over 85,000 different lesions detected 3,253 genes, new entries currently accumulating at rate exceeding 9,000 per annum. Although originally established for scientific study mutational mechanisms HGMD has since...
Abstract Motivation: Advances in high-throughput genotyping and next generation sequencing have generated a vast amount of human genetic variation data. Single nucleotide substitutions within protein coding regions are particular importance owing to their potential give rise amino acid that affect structure function which may ultimately lead disease state. Over the last decade, number computational methods been developed predict whether such result an altered phenotype. Although these useful...
Gorillas are humans' closest living relatives after chimpanzees, and of comparable importance for the study human origins evolution. Here we present assembly analysis a genome sequence western lowland gorilla, compare whole genomes all extant great ape genera. We propose synthesis genetic fossil evidence consistent with placing human–chimpanzee human–chimpanzee–gorilla speciation events at approximately 6 10 million years ago. In 30% genome, gorilla is closer to or chimpanzee than latter...
Abstract Motivation: Technological advances have enabled the identification of an increasingly large spectrum single nucleotide variants within human genome, many which may be associated with monogenic disease or complex traits. Here, we propose integrative approach, named FATHMM-MKL, to predict functional consequences both coding and non-coding sequence variants. Our method utilizes various genomic annotations, recently become available, learns weight significance each component annotation...
Abstract Identifying pathogenic variants and underlying functional alterations is challenging. To this end, we introduce MutPred2, a tool that improves the prioritization of amino acid substitutions over existing methods, generates molecular mechanisms potentially causative disease, returns interpretable pathogenicity score distributions on individual genomes. Whilst its performance state-of-the-art, distinguishing feature MutPred2 probabilistic modeling variant impact specific aspects...
Nonsense mutations account for approximately 11% of all described gene lesions causing human inherited disease and 20% disease-associated single-basepair substitutions affecting coding regions. Pathological nonsense resulting in TGA (38.5%), TAG (40.4%), TAA (21.1%) occur different proportions to naturally occurring stop codons. Of the 23 nucleotide giving rise mutations, most frequent are CGA --> (21%; from methylation-mediated deamination) CAG (19%). The differing mutation frequencies...
We present FATHMM-XF, a method for predicting pathogenic point mutations in the human genome. Drawing on an extensive feature set, FATHMM-XF outperforms competitors benchmark tests, particularly non-coding regions where majority of are likely to be found.The web server is available at http://fathmm.biocompute.org.uk/fathmm-xf/, and as tracks Genome Tolerance Browser: http://gtb.biocompute.org.uk. Predictions provided genome version GRCh37/hg19. The data used this project can downloaded from:...
Although single base-pair substitutions in splice junctions constitute at least 10% of all mutations causing human inherited disease, the factors that determine their phenotypic consequences RNA level remain to be fully elucidated. Employing a neural network for splice-site recognition, we performed meta-analysis 478 disease-associated splicing mutations, 38 different genes, which detailed laboratory-based mRNA phenotype assessment had been performed. Inspection +/-50-bp DNA sequence context...
Metazoan genes are encrypted with at least two superimposed codes: the genetic code to specify primary structure of proteins and splicing expand their proteomic output via alternative splicing. Here, we define specificity a central regulator pre-mRNA splicing, conserved, essential factor SFRS1. Cross-linking immunoprecipitation high-throughput sequencing (CLIP-seq) identified 23,632 binding sites for SFRS1 in transcriptome cultured human embryonic kidney cells. was found engage many...
We have assessed the numbers of potentially deleterious variants in genomes apparently healthy humans by using (1) low-coverage whole-genome sequence data from 179 individuals 1000 Genomes Pilot Project and (2) current predictions databases variants. Each individual carried 281–515 missense substitutions, 40–85 which were homozygous, predicted to be highly damaging. They also 40–110 classified Human Gene Mutation Database (HGMD) as disease-causing mutations (DMs), 3–24 homozygous state, many...
The Human Gene Mutation Database (HGMD) constitutes a comprehensive core collection of data on germ-line mutations in nuclear genes underlying or associated with human inherited disease (http://www.hgmd.org). Data cataloged include single-base-pair substitutions coding, regulatory, and splicing-relevant regions, micro-deletions micro-insertions, indels, triplet repeat expansions, as well gross gene deletions, insertions, duplications, complex rearrangements. Each mutation is entered into...
As the number of non-synonymous single nucleotide polymorphisms (nsSNPs) identified through whole-exome/whole-genome sequencing programs increases, researchers and clinicians are becoming increasingly reliant upon computational prediction algorithms designed to prioritize potential functional variants for further study. A large proportion existing 'disease agnostic' but nevertheless quite capable predicting when a mutation is likely be deleterious. However, most clinical research...
Abstract We introduce MutPred2, a tool that improves the prioritization of pathogenic amino acid substitutions, generates molecular mechanisms potentially causative disease, and returns interpretable pathogenicity score distributions on individual genomes. While its performance is state-of-the-art, novel distinguishing feature MutPred2 probabilistic modeling variant impact specific aspects protein structure function can serve to guide experimental studies phenotype-altering variants....
It is widely accepted that at least 10% of all mutations causing human inherited disease disrupt splice-site consensus sequences. In contrast to mutations, the role auxiliary cis-acting elements such as exonic splicing enhancers (ESE) and silencers (ESS) in still poorly understood. Here we use a top-down approach determine rates loss or gain known regulatory (ESR) sequences associated with either disease-causing putatively neutral single nucleotide polymorphisms (SNPs). We observe...
We have developed a novel machine-learning approach, MutPred Splice, for the identification of coding region substitutions that disrupt pre-mRNA splicing. Applying Splice to human disease-causing exonic mutations suggests 16% causing inherited disease and 10 14% somatic in cancer may For disease, main mechanism responsible splicing defect is splice site loss, whereas predominant disruption predicted be exon skipping via loss enhancers or gain silencer elements. available at...
The cytosine-guanine (CpG) dinucleotide has long been known to be a hotspot for pathological mutation in the human genome. This hypermutability is related its role as major site of cytosine methylation with attendant risk spontaneous deamination 5-methylcytosine (5mC) yield thymine. Cytosine methylation, however, also occurs context CpNpG sites genome, an unsurprising finding since intrinsic symmetry renders it capable supporting semi-conservative model replication pattern. Recently, become...
A new algorithm and Web server, mutation3D (http://mutation3d.org), proposes driver genes in cancer by identifying clusters of amino acid substitutions within tertiary protein structures. We demonstrate the feasibility using a 3D clustering approach to implicate proteins based on explorations single interface. On large scale, we show that with is able separate functional from nonfunctional mutations analyzing combination 8,869 known inherited disease 2,004 SNPs overlaid together upon same...