Our lab develops research software for analyzing large-scale biological datasets. Lab members developed or contributed to the tools below. Also see our GitHub organization.
- TPS: Temporal Pathway Synthesizer
TPS uses protein-protein interactions and time series phosphorylation data to infer signaling pathway structures. It synthesizes (generates) candidate pathways that are consistent with logical constraints. For instance, a protein activated late in a stimulus response cannot control a protein activated earlier in the response. In addition, all proteins in the pathway must be connected to the source(s) of stimulation. Ali Köksal lead the development in collaboration with several other groups.
References: Köksal et al. 2017
- SDREM: Signaling and Dynamic Regulatory Events Miner
SDREM reconstructs the signaling pathways and transcriptional regulatory networks that cells use to response to external stimuli. It takes as input time series gene expression data following stimulation, a list of proteins that initially detect the stimulation, and optional prior knowledge about the relevance of other proteins on the signaling pathway. These condition-specific data are combined with generic protein-protein interactions and protein-DNA interactions (e.g. from ChIP-seq, ChIP-chip, or inferred from DNA binding motifs). The resulting model predicts which transcription factors control the response, when they are active, and how they are activated by upstream signaling pathways. The Gitter et al. 2015 reference below is a step-by-step guide for using the SDREM software (PDF available upon request). MT-SDREM is a multi-task learning extension of SDREM that jointly models multiple responses. The software was developed with Ziv Bar-Joseph’s lab.
- OMICS Integrator
Omics Integrator is a suite of tools for integrating and building network models from multiple types of omic data (transcriptomic, epigenomic, proteomic, genomic, etc.). The Garnet module combines epigenomic and transcriptomic data to determine which transcription factors are relevant in a biological condition. The Forest module uses the prize-collecting Steiner forest (PCSF) algorithm to connect proteins of interest in a protein-protein interaction network, which may optionally include transcription factors from Garnet. The software was primarily developed by Ernest Fraenkel’s lab.
References: Tuncbag et al. 2016
- MEO: Maximum Edge Orientation
MEO orients an undirected graph by finding the edge directions that maximize the high-confidence connections between a set of source nodes and a set of target nodes. This approach can be used to find signaling pathways embedded in a protein-protein interaction network given their starting points (e.g. receptors) and end points (e.g. transcription factors). The software was developed with Ziv Bar-Joseph’s lab.
References: Gitter et al. 2011
- DREM 2.0: Dynamic Regulatory Events Miner
DREM identifies the transcription factors that drive temporal changes in gene expression by predicting which regulators cause groups of genes that are co-expressed up until a particular time point to diverge. It integrates time series gene expression data with protein-DNA interactions (e.g. from ChIP-seq, ChIP-chip, or inferred from DNA binding motifs). DREM 2.0 extends the original DREM by supporting protein-DNA interactions that change over time, incorporating motif finding, and improving the visualization. The software was developed with Jason Ernst and Ziv Bar-Joseph‘s labs.
- Multi-PCSF: Multi-Sample Prize Collecting Steiner Forest
Multi-PCSF extends the PCSF algorithm to jointly model multiple samples or patients. PCSF combines scores on proteins with a weighted protein-protein interaction network to identify low cost connections between high-scoring proteins. The multi-sample extension learns networks for all samples simultaneously, constraining the networks to be similar for different samples. The software was developed with Ernest Fraenkel‘s lab.
References: Gitter et al. 2014