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Full-Text Articles in Molecular Biology

Statistical Analysis Of Genetic Interactions In Tn-Seq Data, Michael A. Dejesus, Subhalaxmi Nambi, Clare M. Smith, Richard E. Baker, Christopher M. Sassetti, Thomas R. Ioerger Feb 2017

Statistical Analysis Of Genetic Interactions In Tn-Seq Data, Michael A. Dejesus, Subhalaxmi Nambi, Clare M. Smith, Richard E. Baker, Christopher M. Sassetti, Thomas R. Ioerger

UMass Metabolic Network Publications

Tn-Seq is an experimental method for probing the functions of genes through construction of complex random transposon insertion libraries and quantification of each mutant's abundance using next-generation sequencing. An important emerging application of Tn-Seq is for identifying genetic interactions, which involves comparing Tn mutant libraries generated in different genetic backgrounds (e.g. wild-type strain versus knockout strain). Several analytical methods have been proposed for analyzing Tn-Seq data to identify genetic interactions, including estimating relative fitness ratios and fitting a generalized linear model. However, these have limitations which necessitate an improved approach. We present a hierarchical Bayesian method for identifying ...


Integrated Genome-Wide Analysis Of Expression Quantitative Trait Loci Aids Interpretation Of Genomic Association Studies, Roby Joehanes, Kahraman Tanriverdi, Jane E. Freedman, Peter J. Munson Jan 2017

Integrated Genome-Wide Analysis Of Expression Quantitative Trait Loci Aids Interpretation Of Genomic Association Studies, Roby Joehanes, Kahraman Tanriverdi, Jane E. Freedman, Peter J. Munson

UMass Metabolic Network Publications

BACKGROUND: Identification of single nucleotide polymorphisms (SNPs) associated with gene expression levels, known as expression quantitative trait loci (eQTLs), may improve understanding of the functional role of phenotype-associated SNPs in genome-wide association studies (GWAS). The small sample sizes of some previous eQTL studies have limited their statistical power. We conducted an eQTL investigation of microarray-based gene and exon expression levels in whole blood in a cohort of 5257 individuals, exceeding the single cohort size of previous studies by more than a factor of 2.

RESULTS: We detected over 19,000 independent lead cis-eQTLs and over 6000 independent lead trans-eQTLs, targeting ...


Comprehensive Essentiality Analysis Of The Mycobacterium Tuberculosis Genome Via Saturating Transposon Mutagenesis, Michael A. Dejesus, Elias R. Gerrick, Weizhen Xu, Sae Woong. Park, Jarukit E. Long, Cara C. Boutte, Eric J. Rubin, Dirk Schnappinger, Sabine Ehrt, Sarah M. Fortune, Christopher M. Sassetti, Thomas R. Ioerger Jan 2017

Comprehensive Essentiality Analysis Of The Mycobacterium Tuberculosis Genome Via Saturating Transposon Mutagenesis, Michael A. Dejesus, Elias R. Gerrick, Weizhen Xu, Sae Woong. Park, Jarukit E. Long, Cara C. Boutte, Eric J. Rubin, Dirk Schnappinger, Sabine Ehrt, Sarah M. Fortune, Christopher M. Sassetti, Thomas R. Ioerger

UMass Metabolic Network Publications

For decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. To date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. As a result, the essentiality of many genomic features, particularly small ones, could not be reliably assessed. We sought to overcome this limitation by creating a completely saturated transposon ...


No Current Evidence For Widespread Dosage Compensation In S. Cerevisiae, Eduardo M. Torres, Michael Springer, Angelika Amon Mar 2016

No Current Evidence For Widespread Dosage Compensation In S. Cerevisiae, Eduardo M. Torres, Michael Springer, Angelika Amon

UMass Metabolic Network Publications

Previous studies of laboratory strains of budding yeast had shown that when gene copy number is altered experimentally, RNA levels generally scale accordingly. This is true when the copy number of individual genes or entire chromosomes is altered. In a recent study, Hose et al. (2015) reported that this tight correlation between gene copy number and RNA levels is not observed in recently isolated wild Saccharomyces cerevisiae variants. To understand the origins of this proposed difference in gene expression regulation between natural variants and laboratory strains of S. cerevisiae, we evaluated the karyotype and gene expression studies performed by Hose ...