Identification of drug compounds for keloids and hypertrophic scars: drug discovery based on text mining and DeepPurpose

Abstract

Background: Keloids (KL) and hypertrophic scars (HS) are forms of abnormal cutaneous scarring characterized by excessive deposition of extracellular matrix and fibroblast proliferation. Currently, the efficacy of drug therapies for KL and HS is limited. The present study aimed to investigate new drug therapies for KL and HS by using computational methods.Methods: Text mining and GeneCodis were used to mine genes closely related to KL and HS. Proteinprotein interaction analysis was performed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape. The selection of drugs targeting the genes closely related to KL and HS was carried out using Pharmaprojects. Drug-target interaction prediction was performed using DeepPurpose, through which candidate drugs with the highest predicted binding affinity were finally obtained.Results: Our analysis using text mining identified 69 KL-and HS-related genes. Gene enrichment analysis generated 25 genes, representing 7 pathways and 130 targeting drugs. DeepPurpose recommended 14 drugs as the final drug list, including 2 phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors, 10 prostaglandin-endoperoxide synthase 2 (PTGS2) inhibitors and 2 vascular endothelial growth factor A (VEGFA) antagonists.Conclusions: Drug discovery using in silico text mining and DeepPurpose may be a powerful and effective way to identify drugs targeting the genes related to KL and HS.

Gene Identification and Potential Drug Therapy for Drug-Resistant Melanoma with Bioinformatics and Deep Learning Technology

“…Three phrases “melanoma,” “drug,” and “resistance” were input into pubmed2ensembl ( http://pubmed2ensembl.ls.manchester.ac.uk/ ), a public source for mining the relevant biological literature on genes, which was used to obtain the associated gene list. We set “Homo sapiens” as the species and selected “Ensembl Gene ID,” “MEDLINE: PubMed ID,” and “Associated Gene Name.” “Search for PubMed IDs” and “filter on Entrez: PMID” were chosen for each query [ 43 – 46 ].…”

“…We set "Homo sapiens" as the species and selected "Ensembl Gene ID," "MEDLINE: PubMed ID," and "Associated Gene Name." "Search for PubMed IDs" and "filter on Entrez: PMID" were chosen for each query [43][44][45][46].…”

“…We summarized the scores of each pair of drugs and target genes. Ultimately, we chose the drugs with affinity scores of at least 7.0 by DAVIS or BindingDB datasets and 12.1 by KIBA dataset [46]. 2.7.…”

Adipose‐derived mesenchymal stem cells‐sourced exosomal microRNA‐7846‐3p suppresses proliferation and pro‐angiogenic role of keloid fibroblasts by suppressing neuropilin 2

“…1,2 However, abnormal proliferation and differentiation of fibroblasts can lead to redundant deposition of ECM and pathological scarring, including hypertrophic scars and keloid. 3,4 The two pathological scars have several adverse consequences such as pain, itching, disfiguring, and motion restriction, though, they have major distinctions in prognosis: hypertrophic scars usually develop within the original wound sites and may regress over time, whereas keloids grow without limitation and barely regress. 5 Nowadays, keloid formation continues to evade the normal wound healing process and remains recalcitrant despite several medical and surgical therapies, including intralesional steroid injection and surgical excision.…”

“…Healthy cutaneous wound healing is a complex and well‐orchestrated process involving hemostasis, inflammation, angiogenesis, granulation tissue formation, reepithelialization, and extracellular matrix (ECM) remodeling 1,2 . However, abnormal proliferation and differentiation of fibroblasts can lead to redundant deposition of ECM and pathological scarring, including hypertrophic scars and keloid 3,4 . The two pathological scars have several adverse consequences such as pain, itching, disfiguring, and motion restriction, though, they have major distinctions in prognosis: hypertrophic scars usually develop within the original wound sites and may regress over time, whereas keloids grow without limitation and barely regress 5 .…”