A5077315066- RNA modifications and cancer
- RNA Research and Splicing
- Gene expression and cancer classification
- Cell Image Analysis Techniques
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Multiple Myeloma Research and Treatments
- Advanced Proteomics Techniques and Applications
- Protein Degradation and Inhibitors
- Viral Infectious Diseases and Gene Expression in Insects
- Ubiquitin and proteasome pathways
- Genetic Mapping and Diversity in Plants and Animals
- Neonatal Respiratory Health Research
- Malaria Research and Control
- Mass Spectrometry Techniques and Applications
- Statistical Methods in Clinical Trials
- Metabolomics and Mass Spectrometry Studies
- Mathematical Biology Tumor Growth
- Cancer-related molecular mechanisms research
- Molecular Biology Techniques and Applications
- Gene Regulatory Network Analysis
- vaccines and immunoinformatics approaches
- Cancer Genomics and Diagnostics
- Neural Networks and Applications
- Fault Detection and Control Systems
Institute for Systems Biology
2023-2025
Systems Biology Institute
2024
Fred Hutch Cancer Center
2018-2021
Science for Life Laboratory
2016-2019
Karolinska Institutet
2015-2019
McGill University and Génome Québec Innovation Centre
2006-2014
McGill University
2013-2014
CEA Grenoble
2013
Université Joseph Fourier
2013
Institut pour l'avancée des biosciences
2013
Abstract mRNA translation plays an evolutionarily conserved role in homeostasis and when dysregulated contributes to various disorders including metabolic neurological diseases cancer. Notwithstanding that optimal universally applicable methods are critical for understanding the complex of translational control under physiological pathological conditions, approaches analyze translatomes largely underdeveloped. To address this, we developed anota2seq algorithm which outperforms current...
Abstract Background DNA microarrays provide data for genome wide patterns of expression between observation classes. Microarray studies often have small samples sizes, however, due to cost constraints or specimen availability. This can lead poor random error estimates and inaccurate statistical tests differential expression. We compare the performance standard t-test, fold change, four n test methods designed circumvent these problems. report results various normalization empirical...
Abstract Background DNA microarrays are popular tools for measuring gene expression of biological samples. This ever increasing popularity is ensuring that a large number microarray studies conducted, many which with data publicly available mining by other investigators. Under most circumstances, validation differential genes performed on to basis. Thus, it not possible generalize results the remaining majority non-validated or evaluate overall quality these studies. Results We present an...
Chronic obstructive pulmonary disease is an independent risk factor for lung cancer, but the underlying molecular mechanisms are unknown. We hypothesized that stromal cells activate pathological gene expression programs support oncogenesis.
Malaria continues to be one of mankind's most devastating diseases despite the many and varied efforts combat it. Indispensable for malaria elimination eventual eradication is development effective vaccines. Controlled human infection (CHMI) an invaluable tool vaccine efficacy assessment investigation early immunological molecular responses against Plasmodium falciparum infection. Here, we investigated gene expression changes following CHMI using RNA-Seq. Peripheral blood samples were...
DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational to determine alternative exon usage (AEU) using such data require impractical visual inspection still yield high false-positive rates. Integrated Gene Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with gene size adjusted false discovery rate exon-level analysis circumvent these limitations. iGEMS was applied two new microarray datasets, including the coverage Human...
iTRAQ and TMT reagent-based mass spectrometry (MS) are commonly used technologies for quantitative proteomics in biological samples. Such studies often performed over multiple MS runs, potentially resulting introduction of run bias that could affect downstream analysis. data have therefore been normalized using a reference sample which is included each run. We show, however, normalization does not effectively remove systematic bias. A linear model approach was previously proposed to improve...
Systematic error is present in all high-throughput screens, lowering measurement accuracy. Because screening occurs at the early stages of research projects, inaccuracy leads to following up inactive features and failing follow active features. Current normalization methods take advantage fact that most primary-screen (e.g., compounds) within each plate are inactive, which permits robust estimates row column systematic-error effects. Screens contain a majority potentially pose more difficult...
Individualized treatment decisions for patients with multiple myeloma (MM) requires accurate risk stratification that takes into account patient-specific consequences of genetic abnormalities and tumor microenvironment on disease outcome therapy responsiveness.
Abstract Motivation: Advantages of statistical testing high-throughput screens include P-values, which provide objective benchmarks compound activity, and false discovery rate estimation. The cost replication required for testing, however, may often be prohibitive. We introduce the single assay-wide variance experimental (SAVE) design whereby a small replicated subset an entire screen is used to derive empirical Bayes random error estimates, are applied remaining majority unreplicated...
The success of high-throughput screening (HTS) strategies depends on the effectiveness both normalization methods and study design. We report comparisons among in two titration series experiments. also extend results a third experiment with differently designed but otherwise identical screens: compounds replicate plates were either placed same well locations or randomly assigned to different locations. Best obtained when randomization was combined that corrected for within-plate spatial...
Abstract Jain et al. introduced the Local Pooled Error (LPE) statistical test designed for use with small sample size microarray gene-expression data. Based on an asymptotic proof, multiplicatively adjusts standard error a of differences between two classes observations by π/2 due to medians rather than means as measures central tendency. The adjustment is upwardly biased at sizes, however, producing fewer expected P-values consequent loss power. We present empirical correction factor which...
ABSTRACT mRNA translation plays an evolutionarily conserved role in homeostasis and when dysregulated results various disorders. Optimal universally applicable analytical methods to study transcriptome-wide changes translational efficiency are therefore critical for understanding the complex of regulation under physiological pathological conditions. Techniques used interrogate translatomes, including polysome- ribosome-profiling, require adjustment total levels capture bona fide alterations...
ABSTRACT Grade IV glioma, formerly known as glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor, its treatment remains challenging in part due to extensive interpatient heterogeneity disease driving mechanisms lack prognostic predictive biomarkers. Using mechanistic inference node-edge relationship (MINER), we have analyzed multiomics profiles from 516 patients constructed an atlas causal drivers GBM (gbmMINER). The has delineated how 30 driver mutations act a...
Rationale: Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer, but the underlying molecular mechanisms are unknown. We hypothesized that stromal cells comprising COPD contain pathological gene expression programs supporting oncogenesis.Objectives: To identify operating in stroma support development of cancer.Methods: Study subjects included patients with (n = 30) or without cancer across a spectrum severity. conducted multi-omics analysis nonmalignant...
Abstract In a phase 3 trial in African infants/children, the RTS,S/AS01 (GSK) vaccine showed moderate efficacy against clinical malaria. We aimed to identify RTS,S/AS01-induced signatures associated with malaria by analyzing antigen-stimulated peripheral blood mononuclear cells sampled from subset of participants at baseline and month (one post-third dose). vaccination was downregulation B-cell monocyte-related transcriptional modules (BTMs) upregulation T-cell related BTMs, as well higher...
Abstract Glioblastoma (GBM) is the most aggressive and lethal type of brain tumor, its treatment remains challenging due to complexity underlying molecular mechanisms. Here, we present gbmMINER, a causal mechanistic transcriptional regulatory network model for GBM that integrates multi-omics clinical data with new quantization approach using MINER algorithm. gbmMINER accurately grouped 9,728 genes into 3,797 regulons identified 179 programs stratify 23 disease states, associated distinct...
Abstract Motivation iTRAQ reagent-based mass spectrometry (MS) is a commonly used technology for identification and quantification of proteins in biological samples. Such studies are often performed over multiple MS runs, potentially resulting introduction run bias that could affect downstream analysis. data have therefore been normalized using reference sample which included each run. We show, however, such normalization does not efficiently remove systematic bias. A linear model approach...