Revealing Drug-Target Interactions with Computational Models and Algorithms

Zhou, Liqian; Li, Zejun; Yang, Jialiang; Tian, Geng; Liu, Fuxing; Chen, Qinghui; Li, Peng; Chen, Min; Ju, Xu; Peng, Lihong

doi:10.3390/molecules24091714

Cited by 54 publications

(31 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although drug-related databases have annotated some DTIs from multiple lines of evidence including experimental data, marketed drug description, and literature mining, more systematic and logic approaches to define DTIs especially in a high-throughput manner are still highly demanded. Artificial intelligence such as machine learning and deep learning has been implemented in several computational tools to predict the potential DTIs at a large scale ( D'Souza et al., 2020 ; Rifaioglu et al., 2019 ; Zhou et al., 2019 ). In addition to database-retrieved information, here we applied two independent computational pipelines to predict de novo DTIs with quantitative measures.…”

Section: Discussionmentioning

confidence: 99%

A computational framework of host-based drug repositioning for broad-spectrum antivirals against RNA viruses

Yao

Cheng

et al. 2021

iScience

View full text Add to dashboard Cite

Summary RNA viruses are responsible for many zoonotic diseases that post great challenges for public health. Effective therapeutics against these viral infections remain limited. Here, we deployed a computational framework for host-based drug repositioning to predict potential antiviral drugs from 2,352 approved drugs and 1,062 natural compounds embedded in herbs of traditional Chinese medicine. By systematically interrogating public genetic screening data, we comprehensively cataloged host dependency genes (HDGs) that are indispensable for successful viral infection corresponding to 10 families and 29 species of RNA viruses. We then utilized these HDGs as potential drug targets and interrogated extensive drug-target interactions through database retrieval, literature mining, and de novo prediction using artificial intelligence-based algorithms. Repurposed drugs or natural compounds were proposed against many viral pathogens such as coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), flaviviruses, and influenza viruses. This study helps to prioritize promising drug candidates for in-depth evaluation against these virus-related diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

A computational framework of host-based drug repositioning for broad-spectrum antivirals against RNA viruses

Yao

Cheng

et al. 2021

iScience

View full text Add to dashboard Cite

show abstract

“…Despite the research progress that has been made in recent years, the pathogenesis mechanisms of autism are still not fully clarified. The development of bioinformatics facilitated the investigation of disease mechanisms and therapeutic strategies (Peng et al, 2017 , 2018 ; Zhou et al, 2019 ). Our study comprehensively elucidated circRNA expression profile in a mouse model of autism and constructed a circRNA-associated ceRNA network.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism

et al. 2021

View full text Add to dashboard Cite

Autism is a common disease that seriously affects the quality of life. The role of circular RNAs (circRNAs) in autism remains largely unexplored. We aimed to detect the circRNA expression profile and construct a circRNA-based competing endogenous RNA (ceRNA) network in autism. Valproate acid was used to establish an in vivo model of autism in mice. A total of 1,059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group was identified by RNA sequencing. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9,715 nodes and 150,408 edges. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. The top three modules were all correlated with autism-related pathways involving “TGF-beta signaling pathway,” “Notch signaling pathway,” “MAPK signaling pathway,” “long term depression,” “thyroid hormone signaling pathway,” etc. The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.

show abstract

“…Although recent target prediction methods have demonstrated that genomic, chemical and pharmacological data can provide reliable information for drug target interaction prediction; those methods often focus solely on the canonical isoforms ("one gene-one protein" model), thereby carrying the risk of ignoring the on-or off-target isoform-level interactions that are related to the compound's activity 68 . Several studies have previously linked cancer specific aberrant splicing with drug resistance mechanisms, for example, BCR-ABL35INS protein with a truncated inactive kinase domain that Imatinib is unable to interact [69][70][71][72] .…”

Section: Discussionmentioning

confidence: 99%

In silico analysis of alternative splicing on drug-target gene interactions

Mishra

Davuluri

2020

Sci Rep

View full text Add to dashboard Cite

full-length protein-coding transcripts, highlighting the complexity of the total proteome that can be expressed by different cells and tissues in the human body. Numerous studies have noted the functional importance of maintaining a coordinated regulation of alternative events in various biological processes, such as tissue development and aging 7-9. Isoforms of a gene often appear to have different, sometimes even opposite functions, and are tightly regulated to express in a context-specific manner. Conversely, a disruption of such coordinated regulation is often linked to diseases, such as cancer. A recent large transcriptome-wide study revealed that ~19% genes consistently undergo isoform switching (context-dependent differential usage of isoforms) that potentially have functional consequences across 12 solid cancer types 10. Such genes with isoform switching were previously found to relate to all hallmarks of cancer, in particular apoptosis and metastasis 11,12. One best example of such aberrant isoform switching in angiogenesis is VEGFA gene, where a switching from anti-angiogenic isoform VEGFA 165 b to pro-angiogenic splice variant VEGFA 165 is observed in multiple types of cancers 13-17. Another apoptosis-related example is the BCL2L1 gene, where a switching from pro-apoptotic short isoform Bcl-xs to anti-apoptotic long splice variant Bcl-xl enable cancer to bypass programmed cell death 18-20. Examples for metastasis-enabling isoform switching include cell surface adhesion receptors, such as CD44 21 and CDH1 (E-cadherin) 22 ; growth factor receptors, such as FGFR2 23 and TGFBR2 24 ; as well as other proteins that induce EMT and confer enhanced invasiveness/motility of cells, such as the Rac1b isoform of RAC1 gene 25-27 and a short-form, constitutively active isoform of RON gene (RonΔ165) 28. Importantly, the RON gene simultaneously produces other tumor-promoting or tumor-opposing isoforms involved in different pathways under different conditions 5. Meanwhile, the aberrant splicing of RAC1 gene has also been linked with multiple other cancer hallmarks, including proliferation, genome instability and inflammation 12. Another aberrant splicing example responsible for sustained proliferative signaling is BRAF gene, as alternative isoforms of wild-type and V600E mutant affect its kinase domain and may confer resistance to treatment 29,30. For isoforms related to evading growth suppressors, human TP53 itself serves as a perfect example, as many splice variants exists for this well-studied tumor suppressor, some of which are dominant-negative hampering anti-tumor function of wild-type p53 31,32. In addition, alternatively spliced, dominant negative isoforms of human telomerase gene TERT were identified in multiple cancers 33,34 , while splice variants for HLA-G protein were found on surface of tumor cells that enhance immune evasion 35. The above examples suggest that disease-causing splice variants, or aberrant isoforms, not only can function as important biomarkers but also have the potential of becoming succes...

show abstract

Revealing Drug-Target Interactions with Computational Models and Algorithms

Cited by 54 publications

References 90 publications

A computational framework of host-based drug repositioning for broad-spectrum antivirals against RNA viruses

A computational framework of host-based drug repositioning for broad-spectrum antivirals against RNA viruses

Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism

In silico analysis of alternative splicing on drug-target gene interactions

Contact Info

Product

Resources

About