Showing 107 of total 107 results (show query)

bioc

MoonlightR:Identify oncogenes and tumor suppressor genes from omics data

Motivation: The understanding of cancer mechanism requires the identification of genes playing a role in the development of the pathology and the characterization of their role (notably oncogenes and tumor suppressors). Results: We present an R/bioconductor package called MoonlightR which returns a list of candidate driver genes for specific cancer types on the basis of TCGA expression data. The method first infers gene regulatory networks and then carries out a functional enrichment analysis (FEA) (implementing an upstream regulator analysis, URA) to score the importance of well-known biological processes with respect to the studied cancer type. Eventually, by means of random forests, MoonlightR predicts two specific roles for the candidate driver genes: i) tumor suppressor genes (TSGs) and ii) oncogenes (OCGs). As a consequence, this methodology does not only identify genes playing a dual role (e.g. TSG in one cancer type and OCG in another) but also helps in elucidating the biological processes underlying their specific roles. In particular, MoonlightR can be used to discover OCGs and TSGs in the same cancer type. This may help in answering the question whether some genes change role between early stages (I, II) and late stages (III, IV) in breast cancer. In the future, this analysis could be useful to determine the causes of different resistances to chemotherapeutic treatments.

Maintained by Matteo Tiberti. Last updated 5 months ago.

dnamethylationdifferentialmethylationgeneregulationgeneexpressionmethylationarraydifferentialexpressionpathwaysnetworksurvivalgenesetenrichmentnetworkenrichment

17 stars 6.57 score

bioc

Moonlight2R:Identify oncogenes and tumor suppressor genes from omics data

The understanding of cancer mechanism requires the identification of genes playing a role in the development of the pathology and the characterization of their role (notably oncogenes and tumor suppressors). We present an updated version of the R/bioconductor package called MoonlightR, namely Moonlight2R, which returns a list of candidate driver genes for specific cancer types on the basis of omics data integration. The Moonlight framework contains a primary layer where gene expression data and information about biological processes are integrated to predict genes called oncogenic mediators, divided into putative tumor suppressors and putative oncogenes. This is done through functional enrichment analyses, gene regulatory networks and upstream regulator analyses to score the importance of well-known biological processes with respect to the studied cancer type. By evaluating the effect of the oncogenic mediators on biological processes or through random forests, the primary layer predicts two putative roles for the oncogenic mediators: i) tumor suppressor genes (TSGs) and ii) oncogenes (OCGs). As gene expression data alone is not enough to explain the deregulation of the genes, a second layer of evidence is needed. We have automated the integration of a secondary mutational layer through new functionalities in Moonlight2R. These functionalities analyze mutations in the cancer cohort and classifies these into driver and passenger mutations using the driver mutation prediction tool, CScape-somatic. Those oncogenic mediators with at least one driver mutation are retained as the driver genes. As a consequence, this methodology does not only identify genes playing a dual role (e.g. TSG in one cancer type and OCG in another) but also helps in elucidating the biological processes underlying their specific roles. In particular, Moonlight2R can be used to discover OCGs and TSGs in the same cancer type. This may for instance help in answering the question whether some genes change role between early stages (I, II) and late stages (III, IV). In the future, this analysis could be useful to determine the causes of different resistances to chemotherapeutic treatments. An additional mechanistic layer evaluates if there are mutations affecting the protein stability of the transcription factors (TFs) of the TSGs and OCGs, as that may have an effect on the expression of the genes.

Maintained by Matteo Tiberti. Last updated 2 months ago.

dnamethylationdifferentialmethylationgeneregulationgeneexpressionmethylationarraydifferentialexpressionpathwaysnetworksurvivalgenesetenrichmentnetworkenrichment

5 stars 6.41 score 43 scripts

bioc

GRaNIE:GRaNIE: Reconstruction cell type specific gene regulatory networks including enhancers using single-cell or bulk chromatin accessibility and RNA-seq data

Genetic variants associated with diseases often affect non-coding regions, thus likely having a regulatory role. To understand the effects of genetic variants in these regulatory regions, identifying genes that are modulated by specific regulatory elements (REs) is crucial. The effect of gene regulatory elements, such as enhancers, is often cell-type specific, likely because the combinations of transcription factors (TFs) that are regulating a given enhancer have cell-type specific activity. This TF activity can be quantified with existing tools such as diffTF and captures differences in binding of a TF in open chromatin regions. Collectively, this forms a gene regulatory network (GRN) with cell-type and data-specific TF-RE and RE-gene links. Here, we reconstruct such a GRN using single-cell or bulk RNAseq and open chromatin (e.g., using ATACseq or ChIPseq for open chromatin marks) and optionally (Capture) Hi-C data. Our network contains different types of links, connecting TFs to regulatory elements, the latter of which is connected to genes in the vicinity or within the same chromatin domain (TAD). We use a statistical framework to assign empirical FDRs and weights to all links using a permutation-based approach.

Maintained by Christian Arnold. Last updated 5 months ago.

softwaregeneexpressiongeneregulationnetworkinferencegenesetenrichmentbiomedicalinformaticsgeneticstranscriptomicsatacseqrnaseqgraphandnetworkregressiontranscriptionchipseq

5.40 score 24 scripts

bioc

RNAdecay:Maximum Likelihood Decay Modeling of RNA Degradation Data

RNA degradation is monitored through measurement of RNA abundance after inhibiting RNA synthesis. This package has functions and example scripts to facilitate (1) data normalization, (2) data modeling using constant decay rate or time-dependent decay rate models, (3) the evaluation of treatment or genotype effects, and (4) plotting of the data and models. Data Normalization: functions and scripts make easy the normalization to the initial (T0) RNA abundance, as well as a method to correct for artificial inflation of Reads per Million (RPM) abundance in global assessments as the total size of the RNA pool decreases. Modeling: Normalized data is then modeled using maximum likelihood to fit parameters. For making treatment or genotype comparisons (up to four), the modeling step models all possible treatment effects on each gene by repeating the modeling with constraints on the model parameters (i.e., the decay rate of treatments A and B are modeled once with them being equal and again allowing them to both vary independently). Model Selection: The AICc value is calculated for each model, and the model with the lowest AICc is chosen. Modeling results of selected models are then compiled into a single data frame. Graphical Plotting: functions are provided to easily visualize decay data model, or half-life distributions using ggplot2 package functions.

Maintained by Reed Sorenson. Last updated 5 months ago.

immunooncologysoftwaregeneexpressiongeneregulationdifferentialexpressiontranscriptiontranscriptomicstimecourseregressionrnaseqnormalizationworkflowstep

4.18 score 2 scripts