ConnecTF: A platform to build gene networks by integrating transcription factor-target gene interactions

Deciphering gene regulatory networks (GRNs) is both a promise and challenge of systems biology. The promise is identifying key transcription factors (TFs) that enable an organism to react to changes in its environment. The challenge is constructing GRNs that involve hundreds of TFs and hundreds of thousands of interactions with their genome-wide target genes validated by high-throughput sequencing. To address this challenge, we developed ConnecTF, a species-independent web-based platform for constructing validated GRNs and to refine inferred GRNs via combined analysis of genome-wide studies of TF-target gene binding, TF-target regulation and other TF-centric omic data. We demonstrate the functionality of ConnecTF in three case studies, showing how integration within and across TF-target datasets uncovers biological insights. Case study 1 uses integration of TF-target gene regulation and binding datasets to uncover mode-of-action and identify potential TF partners for 14 TFs in abscisic acid signaling. Case study 2 demonstrates how genome-wide TF-target data and automated functions in ConnecTF are used to conduct precision/recall analysis and pruning of an inferred GRN for nitrogen signaling. In case study 3, we use ConnecTF to chart a network path from NLP7, a master TF in nitrogen signaling, to direct secondary TF2s, to its indirect targets, in an approach called Network Walking. The public version of ConnecTF (https://ConnecTF.org) contains 3,738,278 TF-target interactions for 423 TFs in Arabidopsis, and 839,210 TF-target interactions for 139 TFs in maize. The database and tools in ConnecTF should advance the exploration of GRNs in plant systems biology applications for models and crops.