KBoost
Reconstructing gene regulatory networks and transcription factor activity is crucial to understand biological processes and holds potential for developing personalized treatment. Yet, it is still an open problem as state-of-art algorithm are often not able to handle large amounts of data. Furthermore, many of the present methods predict numerous false positives and are unable to integrate other sources of information such as previously known interactions. Here we introduce KBoost, an algorithm that uses kernel PCA regression, boosting and Bayesian model averaging for fast and accurate reconstruction of gene regulatory networks. KBoost can also use a prior network built on previously known transcription factor targets. We have benchmarked KBoost using three different datasets against other high performing algorithms. The results show that our method compares favourably to other methods across datasets.
- Repository
- github.com/luisiglm/kboost
Source attribution
- Bioconductor — KBoost
Related resources
Pigengene package provides an efficient way to infer biological signatures from gene expression profiles. The signatures are independent from the underlying platform, e.g., the input can be microarray or RNA Seq data. It can even infer the signatures using data from one platform, and evaluate them on the other. Pigengene identifies the modules (clusters) of highly coexpressed genes using coexpression network analysis, summarizes the biological information of each module in an eigengene, learns a Bayesian network that models the probabilistic dependencies between modules, and builds a decision tree based on the expression of eigengenes.
This package provides methods to efficiently detect competitive endogeneous RNA interactions between two genes. Such interactions are mediated by one or several miRNAs such that both gene and miRNA expression data for a larger number of samples is needed as input. The SPONGE package now also includes spongEffects: ceRNA modules offer patient-specific insights into the miRNA regulatory landscape.
The iNETgrate package provides functions to build a correlation network in which nodes are genes. DNA methylation and gene expression data are integrated to define the connections between genes. This network is used to identify modules (clusters) of genes. The biological information in each of the resulting modules is represented by an eigengene. These biological signatures can be used as features e.g., for classification of patients into risk categories. The resulting biological signatures are very robust and give a holistic view of the underlying molecular changes.
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.
An implementation of a probabilistic modeling framework that jointly analyzes personal genome and transcriptome data to estimate the probability that a variant has regulatory impact in that individual. It is based on a generative model that assumes that genomic annotations, such as the location of a variant with respect to regulatory elements, determine the prior probability that variant is a functional regulatory variant, which is an unobserved variable. The functional regulatory variant status then influences whether nearby genes are likely to display outlier levels of gene expression in that person. See the RIVER website for more information, documentation and examples.
Differential expression analysis of sequence count data. Implements a range of statistical methodology based on the negative binomial distributions, including empirical Bayes estimation, exact tests, generalized linear models, quasi-likelihood, and gene set enrichment. Can perform differential analyses of any type of omics data that produces read counts, including RNA-seq, ChIP-seq, ATAC-seq, Bisulfite-seq, SAGE, CAGE, metabolomics, or proteomics spectral counts. RNA-seq analyses can be conducted at the gene or isoform level, and tests can be conducted for differential exon or transcript usage.