A5085146816- Genomics and Chromatin Dynamics
- Melanoma and MAPK Pathways
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Genomics and Phylogenetic Studies
- Genomics and Rare Diseases
- Cutaneous Melanoma Detection and Management
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Genetic Associations and Epidemiology
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Immunotherapy and Immune Responses
- Chromosomal and Genetic Variations
- Plant Molecular Biology Research
- DNA and Nucleic Acid Chemistry
- Genomic variations and chromosomal abnormalities
- Machine Learning in Bioinformatics
- Pluripotent Stem Cells Research
- Mesenchymal stem cell research
- Genetics and Neurodevelopmental Disorders
- Gene Regulatory Network Analysis
- Fractal and DNA sequence analysis
Illumina (United States)
2022-2024
University of California, Los Angeles
2013-2022
The University of Texas MD Anderson Cancer Center
2018
Broad Center
2015-2017
UCLA Jonsson Comprehensive Cancer Center
2017
Max Planck Institute for Molecular Genetics
2004-2005
Abstract Background DNA methylation is an important epigenetic modification involved in many biological processes. Bisulfite treatment coupled with high-throughput sequencing provides effective approach for studying genome-wide at base resolution. Libraries such as whole genome bisulfite (WGBS) and reduced represented (RRBS) are widely used generating methylomes, demanding efficient versatile tools aligning data. Results We have developed BS-Seeker2, updated version of BS Seeker, a full...
Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding their clinical relevance remains largely incomplete. To systematically decipher the effects human variants, we obtained whole-genome data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these can be inferred to have nondeleterious humans based on presence at high allele...
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic profiling 35 epigenetic modifications transcriptomic analysis, we define chromatin state melanomagenesis by using a cell phenotypic model non-tumorigenic tumorigenic states. Computation specific transitions showed loss histone acetylations H3K4me2/3 on regulatory regions proximal to cancer-regulatory genes in important melanoma-driving signaling pathways. Importantly,...
We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases observed that rare, penetrant mutations in implicated by genome-wide association studies confer ~10-fold larger effects than variants the same genes. Consequently, an individual at phenotypic extreme greatest risk severe, early-onset disease is better identified few rare collective action many weak effects. By combining across phenotype-associated into unified genetic model, we...
Abstract Recently, the first investigation of nucleoli using mass spectrometry led to identification 271 proteins. This represents a rich resource for comprehensive nucleolus evolution. We applied protocol known and novel conserved protein domains nucleolus, resulting in 115 91 domain profiles. The phyletic distribution nucleolar collection complete proteomes selected organisms from all life confirms archaebacterial origin core machinery ribosome maturation assembly, but also reveals...
Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in context melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression human melanocytic neoplasms. Through a series complementary gain-of-function and loss-of-function studies mouse systems, establish oncogenic prometastatic. Mechanistically, RNF2-mediated invasive behavior dependent on its ability to monoubiquitinate H2AK119 at promoter LTBP2, resulting silencing this...
Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well chondrocytes 4 stages in vivo 2 during vitro differentiation. Network analysis delineated five tissue-specific modules; these modules chromatin state defined broad similarities cartilage specification maturation vivo, including progressive silencing...
Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding their clinical relevance remains largely incomplete. To systematically decipher the effects human variants, we obtained whole data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human. We show that these can be inferred to have non-deleterious based on presence at high allele frequencies other...
Expressed Sequence Tags (ESTs) are next to cDNA sequences as the most direct way locate in silico genes of genome and determine their structure. Currently ESTs make up more than 60% all database entries. The goal this work is development a new program called DNA Intelligent Analysis for (DIANA-EST) based on combination Artificial Neural Networks (ANN) statistics characterization coding regions within reconstruction encoded protein.89.7% nucleotides from an independent test set with 127 were...
Accurately predicting the impact of genetic variants is essential for interpreting genomic data, yet no consensus exists on how to measure classifier performance. We prepared most comprehensive set benchmarks date and applied them recently published models PrimateAI-3D AlphaMissense. outperforms AlphaMissense rare-disease cohort biobank benchmarks, indicating that performance clinical databases or in vitro assays does not reliably generalize real-world cohorts.
To model spatial changes of chromatin mark peaks over time we develop and apply ChromTime, a computational method that predicts to be either expanding, contracting, or holding steady between points. Predicted expanding contracting can regulatory regions associated with transcription factor binding gene expression changes. Spatial dynamics provide information about beyond localized signal density ChromTime detects asymmetric expansions contractions, which for some marks associate the...
Genome-wide maps of epigenetic modifications are powerful resources for non-coding genome annotation. Maps multiple epigenetics marks have been integrated into cell or tissue type-specific chromatin state annotations many types. With the increasing availability biologically similar samples, there is a need methods that can effectively summarize information about within groups samples and identify differences across at high resolution.
We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases observed that rare, penetrant mutations in implicated by genome-wide association studies confer ∼10-fold larger effects than variants the same genes. Consequently, an individual at phenotypic extreme greatest risk severe, early-onset disease is better identified few rare collective action many weak effects. By combining across phenotype-associated into unified genetic model, we...
We have developed a web application for the detailed analysis and visualization of evolutionary sequence conservation in complex vertebrate genes. Given pair orthologous genes, protein-coding sequences are aligned. When these mapped back onto their encoding exons genomes, scaffold conserved gene structure naturally emerges. Sequence similarity between introns is analysed embedded into scaffold. The on SVC server provides information about evolutionarily features It further allows concise...
<p>This file contains supplementary methods, figure legends, table legends and references.</p>
<p>Supplementary Figure 1. Western blots. Supplementary 2. Graphs showing tumor volume from mice following intradermal injection of (A) HMEL-BRAF^V600E cells, (B) WM115 (C) 1205 Lu and (D) pMEL-NRAS^G12D overexpressing GFP, RNF2 wild-type or catalytic mutant derivatives (R70C I53S). 3. RNF expression in the melanoma data for normal skin, nevi, primary tumors. 4. Heat map clustering top 10 percent deregulated genes duplicates RNF2^WT compared to GFP cells. 5. Chromatin state analysis on...
<p>Supplementary Figure 1. Western blots. Supplementary 2. Graphs showing tumor volume from mice following intradermal injection of (A) HMEL-BRAF^V600E cells, (B) WM115 (C) 1205 Lu and (D) pMEL-NRAS^G12D overexpressing GFP, RNF2 wild-type or catalytic mutant derivatives (R70C I53S). 3. RNF expression in the melanoma data for normal skin, nevi, primary tumors. 4. Heat map clustering top 10 percent deregulated genes duplicates RNF2^WT compared to GFP cells. 5. Chromatin state analysis on...