Genomic variants-driven drug repurposing for tuberculosis by utilizing the established bioinformatic-based approach

Irham, Lalu Muhammad; Adikusuma, Wirawan; Perwitasari, Dyah Aryani

doi:10.1016/j.bbrep.2022.101334

Cited by 5 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Following the scoring system, a total score equal and greater than two (score ≥ 2) was identified as a DM biological risk gene. In this study, the scoring system was modified based on Okada et al [ 32 ] and applied by Irham et al for several diseases [ 33 , 34 , 35 , 36 , 37 , 38 ]. Next, we used the STRING database to obtain additional DM-targetable genes and the expanded biological DM risk gene.…”

Section: Methodsmentioning

confidence: 99%

Leveraging Genomic and Bioinformatic Analysis to Enhance Drug Repositioning for Dermatomyositis

et al. 2023

Self Cite

View full text Add to dashboard Cite

Dermatomyositis (DM) is an autoimmune disease that is classified as a type of idiopathic inflammatory myopathy, which affects human skin and muscles. The most common clinical symptoms of DM are muscle weakness, rash, and scaly skin. There is currently no cure for DM. Genetic factors are known to play a pivotal role in DM progression, but few have utilized this information geared toward drug discovery for the disease. Here, we exploited genomic variation associated with DM and integrated this with genomic and bioinformatic analyses to discover new drug candidates. We first integrated genome-wide association study (GWAS) and phenome-wide association study (PheWAS) catalogs to identify disease-associated genomic variants. Biological risk genes for DM were prioritized using strict functional annotations, further identifying candidate drug targets based on druggable genes from databases. Overall, we analyzed 1239 variants associated with DM and obtained 43 drugs that overlapped with 13 target genes (JAK2, FCGR3B, CD4, CD3D, LCK, CD2, CD3E, FCGR3A, CD3G, IFNAR1, CD247, JAK1, IFNAR2). Six drugs clinically investigated for DM, as well as eight drugs under pre-clinical investigation, are candidate drugs that could be repositioned for DM. Further studies are necessary to validate potential biomarkers for novel DM therapeutics from our findings.

show abstract

Section: Methodsmentioning

confidence: 99%

Leveraging Genomic and Bioinformatic Analysis to Enhance Drug Repositioning for Dermatomyositis

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the hematopoietic system, CXCR4 binds to its chemokine ligand, CXCL12, to mediate leukocyte transport, distribution, survival, activation, and proliferation. CXCR4 has been reported to help thymic progenitors homing from bone marrow to the thymus and emerges as a promising proposed TB target [75].…”

Section: Tuberculosis-mediated Bone Marrow Hematopoietic Dysfunctionmentioning

confidence: 99%

Possible Mechanisms of Lymphopenia in Severe Tuberculosis

Li,

Chen,

Zeng

et al. 2023

Microorganisms

View full text Add to dashboard Cite

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). In lymphopenia, T cells are typically characterized by progressive loss and a decrease in their count results. Lymphopenia can hinder immune responses and lead to systemic immunosuppression, which is strongly associated with mortality. Lymphopenia is a significant immunological abnormality in the majority of patients with severe and advanced TB, and its severity is linked to disease outcomes. However, the underlying mechanism remains unclear. Currently, the research on the pathogenesis of lymphopenia during M. tuberculosis infection mainly focuses on how it affects lymphocyte production, survival, or tissue redistribution. This includes impairing hematopoiesis, inhibiting T-cell proliferation, and inducing lymphocyte apoptosis. In this study, we have compiled the latest research on the possible mechanisms that may cause lymphopenia during M. tuberculosis infection. Lymphopenia may have serious consequences in severe TB patients. Additionally, we discuss in detail potential intervention strategies to prevent lymphopenia, which could help understand TB immunopathogenesis and achieve the goal of preventing and treating severe TB.

show abstract

“…Single Nucleotide Polimorfism (SNPs) dan perluasan basis data genom berskala besar dengan pemanfaatan Genomic Wide Association Study (GWAS). Studi GWAS melibatkan penanda yang bekerja pada set DNA atau marker pada populasi (Irham et al, 2022). Pada populasi Eropa dan Asia Timur telah ditemukan lebih dari 80 lokus terkait dengan psoriasis (Ogawa and Okada, 2020).…”

Section: Pendahuluanunclassified

Identifikasi Gen Yang Berisiko Untuk Psoriasis Vulgaris Melalui Pemanfaatan Informasi Genomic

Niarisessa,

Puspitaningrum,

Adikusuma

et al. 2023

View full text Add to dashboard Cite

Psoriasis vulgaris merupakan penyakit yang berkaitan dengan autoimun menyebabkan terjadinya inflamasi pada permukaan kulit. Psoriasis vulgaris ditandai dengan adanya plak berwarna merah atau merah muda diselimuti oleh sisik putih atau keabuan. Psoriasis vulgaris mempengaruhi sekitar 2% populasi di Amerika Utara dan Eropa. Kerentanan karena faktor genetik merupakan faktor yang berperan penting dalam terjadinya psoriasis vulgaris. Farmakogenomik berkaitan dengan ilmu yang mempelajari faktor genetik yang mempengaruhi variabilitas respon obat antar individu. Salah satu pemanfaatan farmakogenomik untuk pengembangan biomarker farmakogenomik yang digunakan dalam penemuan obat baru memalui penemuan kandidat gen. Identifikasi variasi gen Single Nucleotide Polimorfism (SNPs) sudah banyak dilakukan sekaligus dikembangkan. Database genomic yang menyimpan data SNPs antara lain Database Genomic Wide Association Study (GWAS) dan Phenom Wide Association Studies (PheWAS). Dalam penelitian ini kami mengidentifiasi 245 SNPs terkait psoriasis vulgaris dengan kriteria r2 < 0.8 untuk populasi asia. Untuk memprioritaskan kandidat gen terkait psoriasis vulgaris, kami menggunakan lima kriteria anotasi fungsional (missense, cis-eQTL, PPI, KEGG, Komice) dimana jika lebih dari dua skor kriteria penilaian, maka didefinisikan sebagai gen resiko biologis psoriasis vulgaris. Sebanyak 52 gen teridentifikasi sebagai gen resiko biologis psoriasis vulgaris. Diperoleh satu gen dengan skor tertinggi 4 yaitu Cluster of differentiation 247 (CD247). Pada penelitian ini dijelaskan potensi genetik sebagai biomarker terhadap kerentanan penyakit psoriasis vulgaris dan juga sebagai target obat. Kata Kunci : Psoriasis Vulgaris, Penyakit autoimun, Variasi Genomik.

show abstract

Genomic variants-driven drug repurposing for tuberculosis by utilizing the established bioinformatic-based approach

Cited by 5 publications

References 40 publications

Leveraging Genomic and Bioinformatic Analysis to Enhance Drug Repositioning for Dermatomyositis

Leveraging Genomic and Bioinformatic Analysis to Enhance Drug Repositioning for Dermatomyositis

Possible Mechanisms of Lymphopenia in Severe Tuberculosis

Identifikasi Gen Yang Berisiko Untuk Psoriasis Vulgaris Melalui Pemanfaatan Informasi Genomic

Contact Info

Product

Resources

About