Abstract
Genome-wide transcriptome profiling after gene perturbation is a powerful means of elucidating gene functional mechanisms in diverse contexts. The comprehensive collection and analysis of the resulting transcriptome profiles would help to systematically characterize context-dependent gene functional mechanisms and conduct experiments in biomedical research. To this end, we collected and curated over 3000 transcriptome profiles in human and mouse from diverse gene perturbation experiments, which involved 1585 different perturbed genes (microRNAs, lncRNAs and protein-coding genes) across 1170 different cell lines/tissues. For each profile, we identified differential genes and their associated functions and pathways, constructed perturbation networks, predicted transcription regulation and cancer/drug associations, and assessed cooperative perturbed genes. Based on these transcriptome analyses, the Gene Perturbation Atlas (GPA) can be used to detect (i) novel or cell-specific functions and pathways affected by perturbed genes, (ii) protein interactions and regulatory cascades affected by perturbed genes, and (iii) perturbed gene-mediated cooperative effects. The GPA is a user-friendly database to support the rapid searching and exploration of gene perturbations. Particularly, we visualized functional effects of perturbed genes from multiple perspectives. In summary, the GPA is a valuable resource for characterizing gene functions and regulatory mechanisms after single-gene perturbations. The GPA is freely accessible at http://biocc.hrbmu.edu.cn/GPA/.
Highlights
Genome-wide transcriptome profiling after gene perturbation is a powerful means of elucidating gene functional mechanisms in diverse contexts
We manually collected and curated 3072 transcriptome profiles of single-gene perturbations measured on microarrays in human and mouse from Gene Expression Omnibus (GEO)
To facilitate the study of context-dependent gene functional mechanisms, we detected (i) novel or cell-specific functions and pathways affected by perturbed genes, (ii) protein interactions and regulatory cascades affected by perturbed genes and (iii) perturbed genes mediating cooperative effects
Summary
Genome-wide transcriptome profiling after gene perturbation is a powerful means of elucidating gene functional mechanisms in diverse contexts. Through analyzing the transcriptome profiles of 147 large intergenic non-coding RNA (lincRNA) knockdowns, Guttman et al revealed that lincRNAs mainly regulated global gene expression in trans, maintained the pluripotency and repressed the differentiation of embryonic stem cells[6] These expression profiles reveal global gene expression changes caused by perturbed genes and can be used to infer their context-dependent biological functions, cellular pathways and regulatory cascades (interacting genes or upstream transcription factors). We collected and analyzed a large number of transcriptome profiles of single-gene perturbations, including protein-coding genes, microRNAs and long non-coding RNAs (lncRNAs), in human and mouse Integrating these profiles and corresponding transcriptome analysis results, we developed a user-friendly database called the Gene Perturbation Atlas (GPA) with several web tools to support rapid searching, exploration and visualization of the gene perturbations. The GPA provides considerable resources, helping biologists to systematically characterize context-dependent gene functions and regulatory mechanisms and providing references for biomedical gene perturbation experiments conducted by experimental scientists
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
