A5023680746- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Cancer-related Molecular Pathways
- Protein Structure and Dynamics
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Genomics and Rare Diseases
- RNA modifications and cancer
- Machine Learning in Bioinformatics
- Computational Drug Discovery Methods
- Head and Neck Cancer Studies
- Genomics and Phylogenetic Studies
- DNA Repair Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Structure and Function
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Evolution and Genetic Dynamics
- Protein Kinase Regulation and GTPase Signaling
- Lung Cancer Treatments and Mutations
- Genetic Associations and Epidemiology
- Circadian rhythm and melatonin
- Neuropeptides and Animal Physiology
Baylor College of Medicine
2016-2025
Baylor Genetics
2002-2024
Quantitative BioSciences
2018-2023
Neurological Research Institute
2013-2023
Texas Children's Hospital
2013-2023
The University of Texas MD Anderson Cancer Center
2018
Oregon Health & Science University
2018
Imperial Valley College
2014-2016
Laboratory of Molecular Genetics
2014
Institute of Molecular Biology and Biophysics
2002-2014
Automated annotation of protein function is challenging. As the number sequenced genomes rapidly grows, overwhelming majority products can only be annotated computationally. If computational predictions are to relied upon, it crucial that accuracy these methods high. Here we report results from first large-scale community-based critical assessment (CAFA) experiment. Fifty-four representing state art for prediction were evaluated on a target set 866 proteins 11 organisms. Two findings stand...
Highlights•871 predisposition variants/CNVs discovered in 8% of 10,389 cases 33 cancers•Pan-cancer approach identified shared variants and genes across cancers•33 affecting activating domains oncogenes showed high expression•47 VUSs prioritized using cancer enrichment, LOH, expression other evidenceSummaryWe conducted the largest investigation to date, discovering 853 pathogenic or likely from types. Twenty-one single cross-cancer associations, including novel associations SDHA melanoma...
Physiological effects of β adrenergic receptor (β2AR) stimulation have been classically shown to result from Gs-dependent adenylyl cyclase activation. Here we demonstrate a novel signaling mechanism wherein β-arrestins mediate β2AR extracellular-signal regulated kinases 1/2 (ERK 1/2) independent G protein Activation ERK1/2 by the expressed in HEK-293 cells was resolved into two components dependent, respectively, on Gs-Gi/protein kinase A (PKA) or β-arrestins. protein-dependent activity...
The TP53 tumor suppressor gene is frequently mutated in human cancers. An analysis of five data platforms 10,225 patient samples from 32 cancers reported by Cancer Genome Atlas (TCGA) enables comprehensive assessment p53 pathway involvement these More than 91% TP53-mutant exhibit second allele loss mutation, chromosomal deletion, or copy-neutral heterozygosity. mutations are associated with enhanced instability, including increased amplification oncogenes and deep deletion genes. Tumors...
Abstract Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation protein function. Results Here, we report on results third CAFA challenge, CAFA3, that featured expanded analysis over previous rounds, both in terms volume data analyzed types performed. In a novel major new development, predictions assessment goals drove some experimental assays, resulting functional annotations for...
Sewing Up DNA Repair All cells have a battery of DNA-repair pathways to help ensure genome maintenance and stability, including stress-induced break repair in Escherichia coli. Similar pathways—which can be mutagenic—are known yeast human the potential accelerate evolution. Sixteen proteins are required for pathway E. Al Mamun et al. (p. 1344 ) analyzed coli determine full complement protein contributions pathway. Ninety-three genes were found repair. One-third identified network involved...
We screened 71 sporadic and 7 familial Rett syndrome (RTT) patients for MECP2 mutations by direct sequencing determined the pattern of X chromosome inactivation (XCI) in 39 RTT patients. identified 23 different disease-causing 54 (76%) 2 (29%) cases. compared electrophysiological findings, cerebrospinal fluid neurochemistry, 13 clinical characteristics between carrying missense those truncating mutations. Thirty-one 34 (91%) with classic had random XCI. Nonrandom XCI was associated milder...
Transmembrane receptors for hormones, neurotransmitters, light, and odorants mediate their cellular effects by activating heterotrimeric guanine nucleotide-binding proteins (G proteins). Crystal structures have revealed contact surfaces between G protein subunits, but not the or molecular mechanism through which Gαβγ responds to activation transmembrane receptors. Such a surface was identified from results of testing 100 mutant α subunits retinal transducin ability interact with rhodopsin....
G protein-coupled receptor (GPCR) activation mediated by ligand-induced structural reorganization of its helices is poorly understood. To determine the universal elements this conformational switch, we used evolutionary tracing (ET) to identify residue positions commonly important in diverse GPCRs. When mapped onto rhodopsin structure, these trace residues cluster into a network contacts from retinal binding site protein-coupling loops. Their roles generic transduction mechanism were...
The pivotal role of G proteins in sensory, hormonal, inflammatory, and proliferative responses has provoked intense interest understanding how they interact with their receptors effectors. Nonetheless, the locations effector binding sites remain poorly characterized, although nearly complete structures alphabetagamma heterotrimeric complex are available. Here we apply evolutionary trace (ET) analysis [Lichtarge, O., Bourne, H. R. & Cohen, F. E. (1996) J. Mol. Biol. 257, 342-358] to...
Keeping up with the ever-expanding flow of data and publications is untenable poses a fundamental bottleneck to scientific progress. Current search technologies typically find many relevant documents, but they do not extract organize information content these documents or suggest new hypotheses based on this organized content. We present an initial case study KnIT, prototype system that mines contained in literature, represents it explicitly queriable network, then further reasons upon...
TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring over two-thirds of cases, but prognostic significance these remains elusive. In current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients tumors harboring as high or low risk, validated this system both vivo vitro models. Patients high-risk had poorest survival outcomes shortest time development distant metastases. Tumor cells...
To assess the impact of somatic gene mutations on survival among patients undergoing resection colorectal liver metastases (CLM).
The relationship between genotype mutations and phenotype variations determines health in the short term evolution over long term, it hinges on action of fitness. A fundamental difficulty determining this action, however, is that depends unique context each mutation, which complex often cryptic. As a result, effect most genome molecular function overall fitness remains unknown stands apart from population genetics theories linking to polymorphism frequency. Here, we hypothesize continuous...
Certain mutations can cause proteins to accumulate in neurons, leading neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration mice. therefore searched for human patients with PUM1 mutations. identified eleven individuals either deletions or de novo missense variants who suffer developmental syndrome (Pumilio1-associated disability,...