A5036380790- Genomics and Chromatin Dynamics
- Bioinformatics and Genomic Networks
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Microbial Metabolic Engineering and Bioproduction
- Immune Cell Function and Interaction
- Gene Regulatory Network Analysis
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- Malaria Research and Control
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Gene expression and cancer classification
- Cancer Immunotherapy and Biomarkers
- SARS-CoV-2 and COVID-19 Research
- Cancer Genomics and Diagnostics
La Jolla Institute for Immunology
2016-2025
University of California, San Diego
2017-2025
University of Georgia
2021
German Cancer Research Center
2020
Heidelberg University
2020
Deutschen Konsortium für Translationale Krebsforschung
2020
University of Washington
2012-2018
École Nationale Supérieure des Mines de Paris
2014
Institut Curie
2014
Inserm
2014
From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation still needed characterize how used help produce functional organism (see Perspective by Blaxter ). In this vein, Gerstein et al. (p. 1775 ) summarize for Caenorhabditis elegans genome, and The modENCODE Consortium 1787 Drosophila melanogaster full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites,...
Our current understanding of how DNA is packed in the nucleus most accurate at fine scale individual nucleosomes and large chromosome territories. However, modeling architecture intermediate ∼50 kb–10 Mb crucial for identifying functional interactions among regulatory elements their target promoters. We describe a method, Fit-Hi-C , that assigns statistical confidence estimates to mid-range intra-chromosomal contacts by jointly random polymer looping effect previously observed technical...
Abstract Motivation: Recent technological advances allow the measurement, in a single Hi-C experiment, of frequencies physical contacts among pairs genomic loci at genome-wide scale. The next challenge is to infer, from resulting DNA–DNA contact maps, accurate 3D models how chromosomes fold and fit into nucleus. Many existing inference methods rely on multidimensional scaling (MDS), which pairwise distances inferred model are optimized resemble derived directly counts. These approaches,...
Abstract Background In mammals, one of the female X chromosomes and all imprinted genes are expressed exclusively from a single allele in somatic cells. To evaluate structural changes associated with allelic silencing, we have applied recently developed Hi-C assay that uses DNase I for chromatin fragmentation to mouse F1 hybrid systems. Results We find radically different conformations two chromosomes. The inactive has superdomains frequent intrachromosomal contacts separated by boundary...
Fewer SARS-CoV-2–reactive memory CD8 + T cells with “exhaustion” features are present in patients severe versus mild COVID-19.
The development of the human malaria parasite Plasmodium falciparum is controlled by coordinated changes in gene expression throughout its complex life cycle, but corresponding regulatory mechanisms are incompletely understood. To study relationship between genome architecture and regulation , we assayed P. at three time points during erythrocytic (asexual) cycle. Using chromosome conformation capture coupled with next-generation sequencing technology (Hi-C), obtained high-resolution...
High numbers of tissue-resident memory T (TRM) cells are associated with better clinical outcomes in cancer patients. However, the molecular characteristics that drive their efficient immune response to tumors poorly understood. Here, single-cell and bulk transcriptomic analysis TRM non-TRM present tumor normal lung tissue from patients revealed PD-1–expressing were clonally expanded enriched for transcripts linked cell proliferation cytotoxicity when compared cells. This feature was more...
HiChIP/PLAC-seq is increasingly becoming popular for profiling 3D chromatin contacts among regulatory elements and annotating functions of genetic variants. Here we describe FitHiChIP, a computational method loop calling from data, which jointly models the non-uniform coverage genomic distance scaling contact counts to compute statistical significance estimates. We also develop technique filter putative bystander loops that can be explained by stronger adjacent loops. Compared existing...
We present MUSTACHE, a new method for multi-scale detection of chromatin loops from Hi-C and Micro-C contact maps. MUSTACHE employs scale-space theory, technical advance in computer vision, to detect blob-shaped objects is scalable kilobase-resolution maps reports that are highly consistent between replicates datasets. Compared other loop callers, such as HiCCUPS SIP, recovers higher number published ChIA-PET HiChIP well linking promoters regulatory elements. Overall, enables an efficient...
Hi-C is currently the most widely used assay to investigate 3D organization of genome and study its role in gene regulation, DNA replication, disease. However, experiments are costly perform involve multiple complex experimental steps; thus, accurate methods for measuring quality reproducibility data essential determine whether output should be further a study. Using real simulated data, we profile performance several recently proposed assessing population including HiCRep, GenomeDISCO,...
Mammalian genomes are partitioned into domains that replicate in a defined temporal order. These can at similar times all cell types (constitutive) or type-specific (developmental). Genome-wide chromatin conformation capture (Hi-C) has revealed sub-megabase topologically associating (TADs), which the structural counterparts of replication domains. Hi-C also segregates inter-TAD contacts 3D spatial compartments align precisely to genome-wide timing profiles. Determinants replication-timing...
Long range regulatory interactions among distal enhancers and target genes are important for tissue-specific gene expression. Genome-scale identification of these in a cell line-specific manner, especially using the fewest possible datasets, is significant challenge. We develop novel computational approach, Regulatory Interaction Prediction Promoters Long-range Enhancers (RIPPLE), that integrates published Chromosome Conformation Capture (3C) data sets with minimal set genomic to predict...
Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference diverse genomics demonstrate their value function expression prediction. We formulate the problem machine-learning framework use both supervised unsupervised to predict edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, expression,...
Abstract Asthma and autoimmune disease susceptibility has been strongly linked to genetic variants in the 17q21 haploblock that alter expression of ORMDL3 ; however, molecular mechanisms by which these perturb gene cell types this effect is most prominent are unclear. We found several overlapped enhancers present mainly primary immune types. CD4 + T cells showed greatest increase (threefold) individuals carrying asthma-risk alleles, where negatively regulated interleukin-2 production. The...
It has long been hypothesized that changes in gene regulation have played an important role human evolution, but regulatory DNA much more difficult to study compared with protein-coding regions. Recent large-scale studies created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional DNA. To better define subject human-specific adaptive we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered 130...
The development of malaria parasites throughout their various life cycle stages is coordinated by changes in gene expression. We previously showed that the three-dimensional organization Plasmodium falciparum genome strongly associated with expression during its replication inside red blood cells. Here, we analyze P. and vivax transmission stages. Major occur localization interactions genes involved pathogenesis immune evasion, host cell invasion, sexual differentiation, master regulation...
Abstract Motivation Eukaryotic chromosomes adapt a complex and highly dynamic three-dimensional (3D) structure, which profoundly affects different cellular functions outcomes including changes in epigenetic landscape gene expression. Making the scenario even more complex, cancer cells harbor chromosomal abnormalities [e.g. copy number variations (CNVs) translocations] altering their genomes both at sequence level of 3D organization. High-throughput chromosome conformation capture techniques...