Bentsen Mette, Heger Vanessa, Schultheis Hendrik, Kuenne Carsten, Looso Mario
Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany.
Comput Struct Biotechnol J. 2022 Jul 21;20:4040-4051. doi: 10.1016/j.csbj.2022.07.025. eCollection 2022.
Cooperativity between transcription factors is important to regulate target gene expression. In particular, the binding grammar of TFs in relation to each other, as well as in the context of other genomic elements, is crucial for TF functionality. However, tools to easily uncover co-occurrence between DNA-binding proteins, and investigate the regulatory modules of TFs, are limited. Here we present TF-COMB (Transcription Factor Co-Occurrence using Market Basket analysis) - a tool to investigate co-occurring TFs and binding grammar within regulatory regions. We found that TF-COMB can accurately identify known co-occurring TFs from ChIP-seq data, as well as uncover preferential localization to other genomic elements. With the use of ATAC-seq footprinting and TF motif locations, we found that TFs exhibit both preferred orientation and distance in relation to each other, and that these are biologically significant. Finally, we extended the analysis to not only investigate individual TF pairs, but also TF pairs in the context of networks, which enabled the investigation of TF complexes and TF hubs. In conclusion, TF-COMB is a flexible tool to investigate various aspects of TF binding grammar.
转录因子之间的协同作用对于调控靶基因表达至关重要。特别是，转录因子彼此之间以及在其他基因组元件背景下的结合语法，对于转录因子的功能至关重要。然而，用于轻松揭示DNA结合蛋白之间共现情况并研究转录因子调控模块的工具有限。在此，我们介绍TF-COMB（使用购物篮分析的转录因子共现）——一种用于研究调控区域内共现转录因子和结合语法的工具。我们发现TF-COMB可以从ChIP-seq数据中准确识别已知的共现转录因子，还能揭示其在其他基因组元件上的优先定位。通过使用ATAC-seq足迹和转录因子基序位置，我们发现转录因子彼此之间呈现出偏好的方向和距离，并且这些具有生物学意义。最后，我们将分析扩展到不仅研究单个转录因子对，还研究网络背景下的转录因子对，这使得能够研究转录因子复合物和转录因子枢纽。总之，TF-COMB是一种灵活的工具，可用于研究转录因子结合语法的各个方面。
