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. 2021 Mar 4;11:5154. doi: 10.1038/s41598-021-84647-2

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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USP7 haploinsufficiency reduces E-protein activity in NCI TARGET T-ALL cohort. (A) NetBID network analysis overview. A transcription factor network was generated based on the transcriptome profiling of T-cell development. Transcription factor activity in T-ALL is estimated using their down-stream targets with NetBID. Dysregulated transcription factors are identified for USP7 haploinsufficiency. (B) NetBID identified transcription factors that interact with TAL1. The edges represent known physical interaction from STRINGdb. (C) Differential activities of TAL1-interacting transcription factors (TF) based on NetBID analysis. The x-axis presents the change in TF activity between USP7^wt and USP7^mut TAL1 T-ALL samples, and the y-axis presents the p-values (− log10) by an unpaired two-sided t test. (D) E2A and HEB activities across the major T-ALL subgroups. (E) Enrichment of E-protein targets in USP7^wt compared to USP7^mut by GSEA analysis. Leading-edge genes are marked by a dotted red rectangle, and the list on the right shows top hit genes.