RTN

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.

This package is a pipeline to identify the key gene regulators in a biological process, for example in cell differentiation and in cell development after stimulation. There are four major steps in this pipeline: (1) differential expression analysis; (2) regulator-target network inference; (3) enrichment analysis; and (4) regulators scoring and ranking.

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.

netZooR unifies the implementations of several Network Zoo methods (netzoo, netzoo.github.io) into a single package by creating interfaces between network inference and network analysis methods. Currently, the package has 3 methods for network inference including PANDA and its optimized implementation OTTER (network reconstruction using mutliple lines of biological evidence), LIONESS (single-sample network inference), and EGRET (genotype-specific networks). Network analysis methods include CONDOR (community detection), ALPACA (differential community detection), CRANE (significance estimation of differential modules), MONSTER (estimation of network transition states). In addition, YARN allows to process gene expresssion data for tissue-specific analyses and SAMBAR infers missing mutation data based on pathway information.

Estimate gene and eQTL networks from high-throughput expression and genotyping assays.

Runs PANDA, an algorithm for discovering novel network structure by combining information from multiple complementary data sources.