A5024467494- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Computational Drug Discovery Methods
- Hormonal Regulation and Hypertension
- Pharmacogenetics and Drug Metabolism
- Gene Regulatory Network Analysis
- Ferroptosis and cancer prognosis
- Glioma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Fibroblast Growth Factor Research
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- Mathematical Biology Tumor Growth
- Molecular Biology Techniques and Applications
- Genetic Associations and Epidemiology
- RNA Research and Splicing
- Colorectal Cancer Treatments and Studies
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Science, Research, and Medicine
- Sex and Gender in Healthcare
- Genetic factors in colorectal cancer
Harvard University
2016-2025
Brigham and Women's Hospital
2022-2024
Harvard University Press
2023
Hospital Sírio-Libanês
2014-2020
Hospital São Paulo
2020
Dana-Farber Cancer Institute
2016-2018
Cancer Research And Biostatistics
2017
Universidade Estadual de Campinas (UNICAMP)
2012-2016
Fundação Getulio Vargas
2014
Although all human tissues carry out common processes, are distinguished by gene expression patterns, implying that distinct regulatory programs control tissue specificity. In this study, we investigate and regulation across 38 profiled in the Genotype-Tissue Expression project. We find network edges (transcription factor to target connections) have higher specificity than nodes (genes) regulating factors) less likely be expressed a tissue-specific manner as compared their targets (genes)....
Sex differences manifest in many diseases and may drive sex-specific therapeutic responses. To understand the molecular basis of sex differences, we evaluated sex-biased gene regulation by constructing sample-specific regulatory networks 29 human healthy tissues using 8,279 whole-genome expression profiles from Genotype-Tissue Expression (GTEx) project. We find network structures each tissue. Even though most transcription factors (TFs) are not differentially expressed between males females,...
Understanding sex differences in colon cancer is essential to advance disease prevention, diagnosis, and treatment. Males have a higher risk of developing lower survival rate than women. However, the molecular features that drive these are poorly understood. In this study, we use both transcript-based gene regulatory network methods analyze RNA-seq data from The Cancer Genome Atlas for 445 patients with cancer. We compared expression between tumors men women observed significant chromosome...
MicroRNAs (miRNAs) are a class of small (∼22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority miRNAs is located within intronic or exonic regions protein-coding genes (host genes), and increasing evidence suggests functional relationship between these their host genes. Here, we introduce miRIAD, web-service to facilitate the analysis genomic structural features intragenic for five species (human, rhesus monkey,...
Characterizing the collective regulatory impact of genetic variants on complex phenotypes is a major challenge in developing genotype to phenotype map. Using expression quantitative trait locus (eQTL) analyses, we constructed bipartite networks which edges represent significant associations between and gene levels found that network structure informs function. We show, 13 tissues, these eQTL are organized into dense, highly modular communities grouping genes often involved coherent...
Gene regulation plays a fundamental role in shaping tissue identity, function, and response to perturbation. Regulatory processes are controlled by complex networks of interacting elements, including transcription factors, miRNAs their target genes. The structure these helps determine phenotypes can ultimately influence the development disease or therapy. We developed GRAND (https://grand.networkmedicine.org) as database for computationally-inferred, context-specific gene regulatory network...
Abstract Inference and analysis of gene regulatory networks (GRNs) require software that integrates multi-omic data from various sources. The Network Zoo (netZoo; netzoo.github.io) is a collection open-source methods to infer GRNs, conduct differential network analyses, estimate community structure, explore the transitions between biological states. netZoo builds on our ongoing development methods, harmonizing implementations in computing languages allow better integration these tools into...
Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response therapy. However, the molecular mechanisms responsible for these disparities not investigated extensively.
Neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery is the preferred treatment strategy for locally advanced rectal cancer. However, complete tumor regression observed in a significant proportion of patients after nCRT, making them ideal candidates alternative strategies to this considerably morbid procedure. Identification such based on clinical findings (complete response - cCR) difficult mainly because it relies subjective and imaging studies. Our goal was identify biomarkers...
Cell lines are an indispensable tool in biomedical research and often used as surrogates for tissues. Although there recognized important cellular transcriptomic differences between cell tissues, a systematic overview of the regulatory processes line those its tissue origin has not been conducted. The RNA-Seq data generated by GTEx project is first available resource which it possible to perform large-scale transcriptional network analysis comparing with their tissues origin. We compared 127...
Although ultrahigh-throughput RNA-Sequencing has become the dominant technology for genome-wide transcriptional profiling, vast majority of RNA-Seq studies typically profile only tens samples, and most analytical pipelines are optimized these smaller studies. However, projects generating ever-larger data sets comprising from hundreds or thousands often collected at multiple centers diverse tissues. These complex present significant challenges due to batch tissue effects, but provide...
Alterations in microRNA (miRNA) processing have been previously linked to aging. Here we used the small molecule enoxacin pharmacologically interfere with miRNA biogenesis and study how it affects aging C. elegans. Enoxacin extended worm lifespan promoted survival under normal oxidative stress conditions. Enoxacin-induced longevity required transcription factor SKN-1/Nrf2 was blunted by antioxidant N-acetyl-cysteine, suggesting a prooxidant-mediated mitohormetic response. The effects of were...
Abstract Lung adenocarcinoma (LUAD) exhibits differences between the sexes in incidence, prognosis, and therapy, suggesting underexplored molecular mechanisms. We conducted an integrative multi-omics analysis using Clinical Proteomic Tumor Analysis Consortium (CPTAC) The Cancer Genome Atlas (TCGA) datasets to contrast transcriptomes proteomes sexes. used TIGER analyze TCGA-LUAD expression data found sex-biased activity of transcription factors (TFs); we PTM-SEA with CPTAC-LUAD proteomics...
Abstract Background: The rising incidence of lung cancer among individuals without a history smoking highlights the need to explore biological mechanisms underlying this phenomenon. Our study aims identify gene regulatory that drive risk never-smokers by analyzing how networks differ between with and cancer, depending on their history. Methods: We used RNA-Seq data from Lung Tissue Research Consortium (LTRC) collected via TOPMed, comprising non-cancerous tissue samples 344 non-small cell...
<h3>Background</h3> Mutations in <i>SPG11</i> are the most frequent known cause of autosomal recessive hereditary spastic paraplegia. Corpus callosum thinning is a hallmark condition but little about damage to other structures CNS. <h3>Objective</h3> To evaluate vivo cerebral patients with mutations. <h3>Methods</h3> 5 and 15 age sex matched healthy controls underwent high resolution diffusion tensor imaging (32 directions) T1 volumetric (1 mm slices) acquisition protocol 3 T scanner...
Summary Sexual dimorphism manifests in many diseases and may drive sex-specific therapeutic responses. To understand the molecular basis of sexual dimorphism, we conducted a comprehensive assessment gene expression regulatory network modeling 31 tissues using 8716 human transcriptomes from GTEx. We observed sexually dimorphic patterns involving as 60% autosomal genes, depending on tissue. Interestingly, sex hormone receptors do not exhibit most tissues; however, differential targeting by...
Enoxacin mitigates obesity by inducing fat and muscle energy metabolism independently of its antibiotic function.
Bipartite network inference is a ubiquitous problem across disciplines. One important example in the field molecular biology gene regulatory inference. Gene networks are an instrumental tool aiding discovery of mechanisms driving diverse diseases, including cancer. However, only noisy observations projections these typically assayed. In effort to better estimate from their projections, we formulate non-convex but analytically tractable optimization called OTTER. This can be interpreted as...
Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and neglected outside these. However, 3' untranslated regions (3' UTR) can also disrupt or create miRNA target sites, trigger oncogene activation tumor suppressor inactivation.We used next-generation sequencing to widely screen for genetic alterations within predicted sites oncogenes associated with colorectal cancer, evaluated functional a new mutation. Target 47 genes was performed 29...
Abstract Glioblastoma is an aggressive cancer of the brain and spine. While analysis glioblastoma ‘omics data has somewhat improved our understanding disease, it not led to direct improvement in patient survival. Cancer survival often characterized by differences gene expression, but mechanisms that drive these are generally unknown. We therefore set out model regulatory associated with inferred individual networks using from two different expression platforms The Genome Atlas. performed...
Compared to men, women often develop COPD at an earlier age with worse respiratory symptoms despite lower smoking exposure. However, most preventive, and therapeutic strategies ignore biological sex differences in COPD. Our goal was better understand sex-specific gene regulatory processes lung tissue the molecular basis for onset severity. We analyzed expression DNA methylation data from 747 individuals Lung Tissue Research Consortium (LTRC), 85 independent dataset. identified...
Gene co-expression measurements are widely used in computational biology to identify coordinated expression patterns across a group of samples. Coordinated genes may indicate that they controlled by the same transcriptional regulatory program, or involved common biological processes. is generally estimated from RNA-Sequencing data, which commonly normalized remove technical variability. Here, we demonstrate certain normalization methods, particular quantile-based can introduce false-positive...