Uncovering cancer gene regulation by accurate regulatory network inference from uninformative data

Deniz Seçilmiş, Thomas Hillerton, Daniel Morgan, Andreas Tjärnberg, Sven Nelander, Torbjörn E.M. Nordling, Erik L.L. Sonnhammer

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4 引文 斯高帕斯(Scopus)

摘要

The interactions among the components of a living cell that constitute the gene regulatory network (GRN) can be inferred from perturbation-based gene expression data. Such networks are useful for providing mechanistic insights of a biological system. In order to explore the feasibility and quality of GRN inference at a large scale, we used the L1000 data where ~1000 genes have been perturbed and their expression levels have been quantified in 9 cancer cell lines. We found that these datasets have a very low signal-to-noise ratio (SNR) level causing them to be too uninformative to infer accurate GRNs. We developed a gene reduction pipeline in which we eliminate uninformative genes from the system using a selection criterion based on SNR, until reaching an informative subset. The results show that our pipeline can identify an informative subset in an overall uninformative dataset, allowing inference of accurate subset GRNs. The accurate GRNs were functionally characterized and potential novel cancer-related regulatory interactions were identified.

原文English
頁(從 - 到)37
頁數1
期刊npj Systems Biology and Applications
6
發行號1
DOIs
出版狀態Published - 2020 11月 9

All Science Journal Classification (ASJC) codes

  • 建模與模擬
  • 生物化學、遺傳與分子生物學 (全部)
  • 藥物發現
  • 電腦科學應用
  • 應用數學

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