Matthew Brush
A5049409463- Biomedical Text Mining and Ontologies
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Semantic Web and Ontologies
- Scientific Computing and Data Management
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Research Data Management Practices
- Endoplasmic Reticulum Stress and Disease
- Radiomics and Machine Learning in Medical Imaging
- Cell Image Analysis Techniques
- Genetics, Bioinformatics, and Biomedical Research
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- Advanced Proteomics Techniques and Applications
- Mitochondrial Function and Pathology
- Trypanosoma species research and implications
- Congenital heart defects research
- Ethics in Clinical Research
- Immune cells in cancer
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
University of North Carolina Health Care
2024
University of Colorado Anschutz Medical Campus
2021-2024
University of North Carolina at Chapel Hill
2024
University of Colorado Denver
2022
Oregon Health & Science University
2012-2021
UCB Pharma (Belgium)
2019
Oregon Clinic
2019
University of California, Los Angeles
2018
Stanford University
2018
Children's Hospital of Philadelphia
2017
The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants be genes that have been characterized, model organisms recapitulate human or veterinary filling evolutionary gaps difficult, many resources must queried to find potentially significant genotype–phenotype associations. Non-human proven instrumental revealing...
The growth arrest and DNA damage-inducible protein, GADD34, associates with protein phosphatase 1 (PP1) promotes in vitro dephosphorylation of the alpha subunit eukaryotic translation initiation factor 2, (eIF-2 alpha). In this report, we show that expression human GADD34 cultured cells reversed eIF-2 phosphorylation induced by thapsigargin tunicamycin, agents promote unfolding endoplasmic reticulum (ER). also okadaic acid but not another inhibitor, calyculin A (CA), which is a result...
The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies provide a representation biomedical knowledge from Open Biological Ontologies (OBO) project adds ability this was derived. We here state several applications using it, such as adding semantic expressivity existing databases, building data entry forms,...
Scientific reproducibility has been at the forefront of many news stories and there exist numerous initiatives to help address this problem. We posit that a contributor is simply lack specificity required enable adequate research reproducibility. In particular, inability uniquely identify resources, such as antibodies model organisms, makes it difficult or impossible reproduce experiments even where science otherwise sound. order better understand magnitude problem, we designed an experiment...
The Cell Ontology (CL) is an OBO Foundry candidate ontology covering the domain of canonical, natural biological cell types. Since its inception in 2005, CL has undergone multiple rounds revision and expansion, most notably representation hematopoietic cells. For vivo cells, focuses on vertebrates but provides general classes that can be used for other metazoans, which subtyped species-specific ontologies. Recent work focused extending various types, developing new modules itself, related...
Abstract In biology and biomedicine, relating phenotypic outcomes with genetic variation environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants be in genes that haven’t been characterized, research organisms recapitulate human or veterinary affecting disease are unknown undocumented, many resources must queried to find potentially significant associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on...
The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical genomic data through both harmonized aggregation federated approaches. decreasing cost sequencing (along with other genome-wide molecular assays) increasing evidence its utility will soon drive generation sequence from tens millions humans, levels diversity. In this perspective, we present GA4GH strategies addressing major challenges revolution. We...
Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study evolution, mechanisms of drug response and resistance, tailoring chemotherapeutic approaches for individual patients. The lack robust standards reporting on PDX has hampered the ability researchers find relevant associated data. Here we present minimal information standard (PDX-MI) generation, quality assurance, use models. PDX-MI defines describing clinical attributes a...
Cell lines have been widely used in biomedical research. The community-based Line Ontology (CLO) is a member of the OBO Foundry library that covers domain cell lines. Since its publication two years ago, significant updates made, including new groups joining CLO consortium, line cells, upper level alignment with (CL) and for Biomedical Investigation, logical extensions. Collaboration among CLO, CL, OBI has established consensus definitions line-specific terms such as ‘cell line’, cell’,...
Abstract Despite progress in the development of standards for describing and exchanging scientific information, lack easy-to-use mapping between different representations same or similar objects databases poses a major impediment to data integration interoperability. Mappings often metadata needed be correctly interpreted applied. For example, are two terms equivalent merely related? Are they narrow broad matches? Or associated some other way? Such relationships mapped not documented, which...
Affinity isolation of protein serine/threonine phosphatases on the immobilized phosphatase inhibitor microcystin-LR identified histone deacetylase 1(HDAC1), HDAC6, and HDAC10 as novel components cellular complexes. Other HDACs, specifically HDAC2, -3, -4, -5, were excluded from such In vitro biochemical studies showed that recombinant but not HDAC4, bound directly to (PP)1 catalytic subunit. No association was observed between HDAC6 PP2A, another major phosphatase. PP1 binding mapped second...
<ns4:p>A central tenet in support of research reproducibility is the ability to uniquely identify resources, i.e., reagents, tools, and materials that are used perform experiments. However, current reporting practices for resources insufficient allow humans algorithms exact reported or answer basic questions such as “What other studies resource X?” To address this issue, Resource Identification Initiative was launched a pilot project improve standards methods sections papers thereby...
The principles of genetics apply across the entire tree life. At cellular level we share biological mechanisms with species from which diverged millions, even billions years ago. We can exploit this common ancestry to learn about health and disease, by analyzing DNA protein sequences, but also through observable outcomes genetic differences, i.e. phenotypes. To solve challenging disease problems need unify heterogeneous data that relates genomics traits. Without a big-picture view phenotypic...
ATP synthase, H+ transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a of synthase and plays an important role in coupling proton translocation production. Here, we describe two individuals, each with homozygous missense variants ATP5F1D, who presented episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, hyperammonemia. Subject 1, for c.245C>T (p.Pro82Leu), recurrent decompensation starting the neonatal period, subject 2, c.317T>G (p.Val106Gly),...
SMARCC2 (BAF170) is one of the invariable core subunits ATP-dependent chromatin remodeling BAF (BRG1-associated factor) complex and plays a crucial role in embryogenesis corticogenesis. Pathogenic variants genes encoding other components have been associated with intellectual disability syndromes. Despite its significant biological role, not directly human disease previously. Using whole-exome sequencing web-based gene-matching program, we identified 15 individuals variable degrees...
Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they processed made available comply with ethical regulatory frameworks informed consent data conditions. To enable streamline access these datasets, the Global Alliance Genomics Health (GA4GH) Data Use Researcher Identities (DURI) work stream developed approved...
Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh remain poorly understood. Exome sequencing families with polymicrogyria (disordered cortical folding) revealed individuals biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye and spinal cord patterning changes...
Zipper-interacting protein kinase (ZIPK) regulates Ca(2+)-independent phosphorylation of both smooth muscle (to regulate contraction) and non-muscle myosin non-apoptotic cell death) through either inhibition phosphatase, the phosphatase inhibitor CPI17, or direct light chain. ZIPK is regulated by multisite phosphorylation. Phosphorylation at least three sites Thr-180, Thr-225, Thr-265 has been shown to be essential for full activity, whereas Thr-299 its intracellular localization. Herein we...