Omics A Journal of Integrative Biology最新文献

{"title":"Explaining Type 2 Diabetes with Transcriptomic Signatures of Pancreatic β-Cell Dysfunction and Death Induced by Human Islet Amyloid Polypeptide.","authors":"Pratiksha H Roham, Saurabh Singh Yadav, Brindha Senthilnathan, Pranjali Potdar, Sujata Roy, Shilpy Sharma","doi":"10.1089/omi.2024.0216","DOIUrl":"https://doi.org/10.1089/omi.2024.0216","url":null,"abstract":"<p><p>Amyloid deposits formed by misfolding and aggregation of human islet amyloid polypeptide (hIAPP) are one of the key pathophysiological features of type 2 diabetes mellitus (T2DM) and have been associated with the loss of function and viability of the pancreatic β-cells. The molecular processes by which hIAPP induces cytotoxicity in these cells are not well understood. To the best of our knowledge, this is the first report describing findings from the combined analysis of Affymetrix microarray and high-throughput sequencing (HTS) Gene Expression Omnibus (GEO) datasets of h<i>IAPP</i>-transgenic (Tg) mice islets. In brief, using GEO data, we compared <i>in silico</i> the pancreatic islets obtained from h<i>IAPP</i>-Tg and wild-type mice. Affymetrix microarray datasets (GSE84423, GSE85380, and GSE94672) and HTS datasets (GSE135276 and GSE148809) were chosen. Weighted gene coexpression network analysis was performed using GSE135276 to identify the coexpressed gene networks and establish a correlation pattern between gene modules and h<i>IAPP</i> overexpression under hyperglycemic conditions. Subsequently, we analyzed differential gene expression with the remaining datasets. Network analysis was performed to identify hub genes and the associated pathways using Cytoscape. Key findings from the present study include identification of seven hub genes, namely, <i>Ins2</i>, <i>Agt</i>, <i>Jun</i>, <i>Fos</i>, <i>CD44</i>, <i>Igf1</i>, and <i>Ppar-γ</i>, significantly involved in the process(es) of insulin synthesis and secretion, development of insulin resistance, oxidative stress, inflammation, mitophagy, and apoptosis. In conclusion, we propose that these hub genes can help explain T2DM pathogenesis and can be potentially utilized to develop therapeutic interventions targeting hIAPP for clinical management of T2DM.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Design in the Age of Network Medicine and Systems Biology: Transcriptomics Identifies Potential Drug Targets Shared by Sarcoidosis and Pulmonary Hypertension.","authors":"Sanjukta Dasgupta","doi":"10.1089/omi.2025.0031","DOIUrl":"https://doi.org/10.1089/omi.2025.0031","url":null,"abstract":"<p><p>Network medicine considers the interconnectedness of human diseases and their underlying molecular substrates. In this context, sarcoidosis and pulmonary hypertension (PH) have long been thought of as distinct diseases, but there is growing evidence of shared molecular mechanisms. This study reports on common differentially expressed genes (DEGs), regulatory elements, and pathways between the two diseases. Publicly available transcriptomic datasets for sarcoidosis (GSE157671) and PH (GSE236251) were retrieved from the Gene Expression Omnibus database. DEGs were identified using GEO2R, followed by pathway enrichment and gene interaction analyses via GeneMANIA and STRING. Importantly, a total of 13 common DEGs were identified between sarcoidosis and PH, with 7 upregulated and 6 downregulated genes. The SMAD2/3 nuclear pathway was a shared enriched pathway, suggesting a role in fibrosis and immune regulation. There were also divergences between sarcoidosis and PH. For example, gene set enrichment analysis indicated significant associations of the IFN-gamma signaling pathway with sarcoidosis and the TNF-alpha signaling with PH. miRNA network analysis identified hsa-miR-34a-5p, hsa-let-7g-5p, and hsa-miR-19a-3p as key shared regulators linked to common genes in both sarcoidosis and PH. Finally, DGIdb analysis revealed potential therapeutic candidates targeting these genes in both diseases. This study contributes to the field of drug design and discovery from a network medicine standpoint. The shared molecular links uncovered between sarcoidosis and PH in this study point to several potential biomarkers and therapeutic targets. Further experimental validation and translational medical research are called for diagnostics and drugs, which can effectively and safely help the clinical management of both diseases.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Human Holobiome and Meta-Multi-Omics Analyses for Medical Applications.","authors":"Muhammed Erkan Karabekmez","doi":"10.1089/omi.2025.0024","DOIUrl":"https://doi.org/10.1089/omi.2025.0024","url":null,"abstract":"<p><p>Next-generation sequencing technology has revolutionized all fields of living systems, and its applications almost reinvented some research areas including metagenomics. The microbiotas in our body, including those of the oral, nasal, ocular, alveolar, skin regions, and particularly gut microbiota, have close linkages with our health status. Maturation of experimental techniques for metagenomics has been followed by other related omics platforms, for example, metatranscriptomics, metaproteomics, and all possible metacounterparts of multiomics studies. Now, we are on the eve of a meta-multi-omics era for the analysis of human holobiome in medical research. This era will help buttress the current efforts for systems medicine by illuminating the relationships between human holobiome and health or all human diseases including not only cancers but also infectious diseases, autoimmune diseases, obesity, aging, genetic disorders, and psychiatric conditions. Equally important, meta-multi-omics era is also poised to inform the determinants of human health and, by extension, help build individually tailored precision medicine interventions.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Overlapping Genetic Signatures Between Obstructive Sleep Apnea and Lung Cancer: Moving Beyond \"One Drug, One Disease\" Paradigm of Pharmaceutical Innovation.","authors":"Sanjukta Dasgupta","doi":"10.1089/omi.2025.0010","DOIUrl":"https://doi.org/10.1089/omi.2025.0010","url":null,"abstract":"<p><p>Traditional paradigms of pharmaceutical innovation have long relied on the \"one drug, one disease\" premise. However, a network mindset in unpacking disease mechanisms can be fruitful to move toward a \"one drug, polydisease\" paradigm of drug discovery and development. A case in point is obstructive sleep apnea (OSA) and lung cancer, which are two prevalent respiratory disorders that share common risk factors and may potentially exhibit overlapping molecular mechanisms. The putative mechanistic linkages between OSA and lung cancer remain underexplored; however, this study offers new evidence on overlapping genetic signatures between OSA and lung cancer with an in-silico approach. Bioinformatics analysis of the publicly available datasets (GSE135917 and GSE268175) identified 123 upregulated and 13 downregulated genes in OSA and 3175 upregulated and 2272 downregulated genes in lung cancer. A total of four genes (<i>C1GALT1</i>, <i>TMEM106B</i>, <i>ZNF117</i>, and <i>ZNF486</i>) were significantly upregulated with both disorders, highlighting potentially shared genetic and molecular mechanisms. Pathway and cell enrichment analysis indicated that mucin type O-glycan biosynthesis pathway and endothelial cells are strongly associated with these shared genes, lending support for their potential roles in both diseases. Moreover, hsa-miR-34a-5p, hsa-let-7g-5p, and hsa-miR-19a-3p were found to be associated with these common genes. Validation using the GEPIA2 tool confirmed the consistent expression patterns of these four genes in lung cancer. Machine learning analysis highlighted <i>TMEM106B</i> as the most significant biomarker candidate for distinguishing OSA and lung cancer from controls. In summary, this study supports the overarching concept that human diseases can have shared mechanistic pathways in the specific example of OSA and lung cancer. While these findings call for further research and validation, they invite rethinking the current pharmaceutical innovation paradigms to move beyond the \"one drug, one disease\" concept.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orchestrating Intracellular Calcium Signaling Cascades by Phosphosite-Centric Regulatory Network: A Comprehensive Analysis on Kinases CAMKK1 and CAMKK2.","authors":"Althaf Mahin, Athira Perunelly Gopalakrishnan, Mukhtar Ahmed, Mahammed Nisar, Levin John, Prathik Basthikoppa Shivamurthy, Samseera Ummar, Susmi Varghese, Prashant Kumar Modi, Vinitha Ramanath Pai, Thottethodi Subrahmanya Keshava Prasad, Rajesh Raju","doi":"10.1089/omi.2024.0196","DOIUrl":"10.1089/omi.2024.0196","url":null,"abstract":"<p><p>Intracellular calcium signaling is a cornerstone in cell biology and a key molecular target for human health and disease. Calcium/calmodulin dependent protein kinase kinases, CAMKK1 and CAMKK2 are serine/threonine kinases that contribute to the regulation of intracellular calcium signals in response to diverse stimuli. CAMKK1 generally has stable dynamics, whereas CAMKK2 dysregulation triggers oncogenicity and neurological disorders. To differentiate the phosphosignaling hierarchy associated with predominant phosphosites of CAMKK1 and CAMKK2, we assembled and analyzed the global cellular phosphoproteome datasets. We found that predominant phosphosites in CAMKK1 and CAMKK2 are located outside the kinase domain, and their phosphomotifs are highly homologous. Further, we employed a coregulation analysis approach to these predominant phosphosites, to infer the co-occurrence patterns of phosphorylations within CAMKKs and the coregulation patterns of other protein phosphosites with CAMKK sites. We report herein that independent phosphorylations at CAMKK2 S100 and S511 increase their enzymatic activity in the presence of calcium/calmodulin. In addition, the study unveils kinase-substrate associations such as RPS6KB1 as a novel high-confidence upstream kinase of both CAMKK1 S74 and CAMKK2 S100. Further, CAMKK2 was identified as a primary orchestrator in mediating intracellular calcium signaling cascades compared to CAMKK1 based on coregulation patterns of phosphosites from proteins involved in the calcium signaling pathway. These molecular details shed promising insights into the pathophysiology of several diseases such as cancers and psychiatric disorders associated with kinase activity dysregulations of CAMKK2 and further open the avenue for novel PTM-directed therapeutic strategies to regulate CAMKK2.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"139-153"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Genetic Ancestry on Phenotypes and Genotypes in Papillary Thyroid Cancer.","authors":"Shun-Yu Chi, Yi-Chiung Hsu, Shih-Ping Cheng","doi":"10.1089/omi.2024.0189","DOIUrl":"10.1089/omi.2024.0189","url":null,"abstract":"<p><p>Thyroid cancer (THCA) is a prevalent health burden, and unpacking its biological and social determinants is a public health priority. Previous studies have reported inconsistent findings regarding the effects of race and ethnicity on the incidence and presentation of THCA. It remains unclear whether racial differences manifest at the molecular level. By harnessing the Cancer Genome Atlas papillary THCA dataset, this study derived genetic ancestry estimates from single nucleotide polymorphism array genotyping and exome sequencing data. Five ancestral groups (Europeans, East Asians, Africans, Native/Latin Americans, and South Asians) were included for analysis. We found a good agreement between genetic ancestry and reported race (Cramer's V = 0.730). Although differences in tumor size and patient age were observed, overall survival, progression-free interval, and disease-free interval were similar across the ancestral groups. Furthermore, the distribution of oncogenic drivers did not significantly differ among these groups. Weighted gene co-expression network analysis identified several ancestry-associated signatures. In conclusion, this study suggests that hereditary ancestral traits likely have little biological significance in papillary THCA. Instead, racial disparities in this type of cancer may be attributed to lifestyle factors, environmental exposures, and social and political power asymmetries in society and healthcare infrastructure.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"117-124"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theranostic Target NSUN2, a C(5)-Methyltransferase, Phospho-Regulatory Network Uncovered with Systematic Assembly of 805 Datasets.","authors":"Fathimathul Lubaba, Mejo George, Mukhtar Ahmed, Levin John, Athira Perunelly Goplakrishnan, Prathik Basthikoppa Shivamurthy, Susmi Varghese, Priyanka Pahal, Mahammad Nisar, Poornima Ramesh, Inamul Hasan Madar, Rajesh Raju","doi":"10.1089/omi.2025.0025","DOIUrl":"10.1089/omi.2025.0025","url":null,"abstract":"<p><p>The RNA cytosine C(5)-methyltransferase NSUN2 is involved in RNA modification and regulates gene expression and genomic stability. Beyond multiple sequence/copy number variations, NSUN2 displays altered phosphoprotein expression in various cancers and developmental disorders, thereby making it a prime molecular target of relevance to both therapeutics and diagnostics, that is, theranostics. Despite its key role in kinase-regulated pathways and broader biological processes, the phospho-regulatory network of NSUN2 remains largely unexplored. We report here a systematic assembly of 805 phosphoproteomics datasets from the literature, among which 239 datasets showed differential regulation of NSUN2 phosphopeptides and 40 ensembled phosphosites in NSUN2. Significantly, the phosphorylation sites Ser456, Ser743, and Ser751 represented NSUN2 in ∼50% of these datasets. This is notable given that the functional roles of these phosphosites have been previously underappreciated and underrepresented in the scientific literature. Therefore, we implemented a codetection/coregulation approach based on the phosphosites in other proteins that are codifferentially regulated with phosphopeptides of NSUN2. This approach led to our identification of 55 interactors, 4 potential kinases, and 7 other methylases whose phosphopeptides were codifferentially regulated with NSUN2 phosphopeptides. To the best of our knowledge, this study provides the first phosphosite-centric regulatory network model of NSUN2 to employ theranostic strategies for targeting NSUN2 in cancers and other disorders.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"164-177"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Scale Metabolic Modeling of Human Pancreas with Focus on Type 2 Diabetes.","authors":"Mustafa Sertbas, Kutlu O Ulgen","doi":"10.1089/omi.2024.0211","DOIUrl":"10.1089/omi.2024.0211","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is characterized by relative insulin deficiency due to pancreatic beta cell dysfunction and insulin resistance in different tissues. Not only beta cells but also other islet cells (alpha, delta, and pancreatic polypeptide [PP]) are critical for maintaining glucose homeostasis in the body. In this overarching context and given that a deeper understanding of T2D pathophysiology and novel molecular targets is much needed, studies that integrate experimental and computational biology approaches offer veritable prospects for innovation. In this study, we report on single-cell RNA sequencing data integration with a generic Human1 model to generate context-specific genome-scale metabolic models for alpha, beta, delta, and PP cells for nondiabetic and T2D states and, importantly, at single-cell resolution. Moreover, flux balance analysis was performed for the investigation of metabolic activities in nondiabetic and T2D pancreatic cells. By altering glucose and oxygen uptakes to the metabolic networks, we documented the ways in which hypoglycemia, hyperglycemia, and hypoxia led to changes in metabolic activities in various cellular subsystems. Reporter metabolite analysis revealed significant transcriptional changes around several metabolites involved in sphingolipid and keratan sulfate metabolism in alpha cells, fatty acid metabolism in beta cells, and myoinositol phosphate metabolism in delta cells. Taken together, by leveraging genome-scale metabolic modeling, this research bridges the gap between metabolic theory and clinical practice, offering a comprehensive framework to advance our understanding of pancreatic metabolism in T2D, and contributes new knowledge toward the development of targeted precision medicine interventions.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"125-138"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seven Hub Genes Associated with Huntington's Disease and Diagnostic and Therapeutic Potentials Identified by Computational Biology.","authors":"Afzal Hussain, Taj Mohammad, Shumayila Khan, Mohamed F Alajmi, Dharmendra Kumar Yadav, Md Imtaiyaz Hassan","doi":"10.1089/omi.2025.0006","DOIUrl":"10.1089/omi.2025.0006","url":null,"abstract":"<p><p>Huntington's disease (HD) is characterized by progressive motor dysfunction and cognitive decline. Early diagnosis and new therapeutic targets are essential for effective interventions. We performed integrative analyses of mRNA profiles from three microarrays and one RNA-seq dataset from the Gene Expression Omnibus database. The datasets included were GSE8762, GSE24250, GSE45516, and GSE64810. Data pre-processing included background correction, normalization, log2 transformation, probe-to-gene symbol mapping, and differential expression analysis. We identified 80 differentially expressed genes (DEGs) based on a significance threshold (<i>p</i> < 0.05) and absolute log fold change (logFC) >0.65. Additionally, we conducted Gene Ontology (GO) and pathway analyses of the identified genes. Protein-protein interactions among DEGs revealed a network from which seven hub genes (<i>VIM, COL1A1, COL3A1, COL1A2, DCN, CXCR2,</i> and <i>S100A9</i>) were identified using the cytoHubba plugin in Cytoscape software. Two top DEGs, <i>IGHG1</i> (up-regulated) and <i>PITX1</i> (up-regulated), also hold potential as therapeutic targets. Insofar as biological contextualization of the findings is concerned, the top enriched GO terms were skeletal system development, blood vessel development, and vasculature development. Molecular function terms highlighted signaling receptor binding, extracellular matrix structural constituent, and platelet-derived growth factor binding. Notably, the significant KEGG pathways included amoebiasis, the AGE-RAGE signaling pathway in diabetic complications, and the relaxin signaling pathway. In conclusion, the present computational biology integrative analyses of multiple datasets discovered new DEGs and seven hub genes, shedding light on molecular mechanisms of HD. These findings call for translational clinical omics research and may potentially lead to future precision medicine interventions and novel diagnostic biomarkers and therapeutic targets.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"154-163"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Idiopathic Pulmonary Fibrosis: <i>In Silico</i> Therapeutic Potential of Doxycycline, Pirfenidone, and Nintedanib, and the Role of Next-Generation Phenomics in Drug Discovery.","authors":"Sanjukta Dasgupta","doi":"10.1089/omi.2024.0213","DOIUrl":"10.1089/omi.2024.0213","url":null,"abstract":"<p><p>Innovation in drug discovery for human diseases stands to benefit from systems science and next-generation phenomics approaches. An example is idiopathic pulmonary fibrosis (IPF) that is a chronic pulmonary disorder leading to respiratory failure and for which preventive and therapeutic medicines are sorely needed. Matrix metalloproteinases (MMPs), particularly MMP1 and MMP7, have been associated with IPF pathogenesis and are thus relevant to IPF drug discovery. This study evaluates the comparative therapeutic potentials of doxycycline, pirfenidone, and nintedanib in relation to MMP1 and MMP7 using molecular docking, molecular dynamics simulations, and a next-generation phenomics approach. Adsorption, distribution, metabolism, excretion, and toxicity analysis revealed that doxycycline and nintedanib adhered to Lipinski's rule of five, while pirfenidone exhibited no violations. The toxicity analysis revealed favorable safety profiles, with lethal dose 50 values of doxycycline, pirfenidone, and nintedanib being 2240kg, 580, and 500 mg/kg, respectively. Homology modeling validated the accuracy of the structures of the target proteins, that is, MMP1 and MMP7. The Protein Contacts Atlas tool, a next-generation phenomics platform that broadens the scope of phenomics research, was employed to visualize protein contacts at atomic levels, revealing interaction surfaces in MMP1 and MMP7. Docking studies revealed that nintedanib exhibited superior binding affinities with the candidate proteins (-6.9 kcal/mol for MMP1 and -7.9 kcal/mol for MMP7) compared with doxycycline and pirfenidone. Molecular dynamics simulations further demonstrated the stability of protein-ligand complexes. These findings highlight the notable potential of nintedanib in relation to future IPF therapeutics innovation. By integrating <i>in silico</i> and a next-generation phenomics approach, this study opens up new avenues for drug discovery and development for IPF and possibly, for precision/personalized medicines that consider the molecular signatures of therapeutic candidates for each patient.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"87-95"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}