Multi-Omic Metabolic Enrichment Network Analysis reveals metabolite-protein physical interaction subnetworks altered in cancer

Nationalism is an issue that is often contested in a political rally in various countries. Nationalism is generally used to describe two phenomena: first, the attitude of members of the nation when they care about their national identity. Second, it can be defined as any action performed by members of the nation to sustain their self-determination or political sovereignty. In the era of conventional media, nationalism was created from the dynamics of physical interaction, human to human. However, in the new media era, nationalism has turned into "human to technology to human". This leads to a dynamic that never happened before. To capture this, online news and social media data were captured using the SNA (Social Network Analysis) method, in collaboration with astramaya.id that saw 19 online news items listed. Data were also collected from Facebook (3,376 mentions), Instagram (3,417 mentions), Twitter (160,432 mentions), and YouTube (1,699 mentions). The time frame, July 2019 to July 2020, takes into account the high level of discussion on nationalism after the presidential election and Covid-19. This research found that: first, Indonesia’s Nationalism has divided into two caps; second, a non-human social media account gives a significant contribution to these cleavages; third, primordial sentiments take determining effect for every actor in generating cleavage. Keywords: Nationalism, online news, social media, social network analysis, Indonesia.

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Integrative network analysis reveals USP7 haploinsufficiency inhibits E-protein activity in pediatric T-lineage acute lymphoblastic leukemia (T-ALL)

Scientific Reports ◽

10.1038/s41598-021-84647-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Timothy I. Shaw ◽

Li Dong ◽

Liqing Tian ◽

Chenxi Qian ◽

Yu Liu ◽

...

Keyword(s):

Network Analysis ◽

Target Genes ◽

Lymphoblastic Leukemia ◽

Cancer Therapeutics ◽

Physical Interaction ◽

Loss Of Function ◽

Protein Activity ◽

E Proteins ◽

Down Regulation ◽

E Protein

AbstractUSP7, which encodes a deubiquitylating enzyme, is among the most frequently mutated genes in pediatric T-ALL, with somatic heterozygous loss-of-function mutations (haploinsufficiency) predominantly affecting the subgroup that has aberrant TAL1 oncogene activation. Network analysis of > 200 T-ALL transcriptomes linked USP7 haploinsufficiency with decreased activities of E-proteins. E-proteins are also negatively regulated by TAL1, leading to concerted down-regulation of E-protein target genes involved in T-cell development. In T-ALL cell lines, we showed the physical interaction of USP7 with E-proteins and TAL1 by mass spectrometry and ChIP-seq. Haploinsufficient but not complete CRISPR knock-out of USP7 showed accelerated cell growth and validated transcriptional down-regulation of E-protein targets. Our study unveiled the synergistic effect of USP7 haploinsufficiency with aberrant TAL1 activation on T-ALL, implicating USP7 as a haploinsufficient tumor suppressor in T-ALL. Our findings caution against a universal oncogene designation for USP7 while emphasizing the dosage-dependent consequences of USP7 inhibitors currently under development as potential cancer therapeutics.

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