Omics A Journal of Integrative Biology最新文献

{"title":"How Can We Boost the Pharmacogenomics Adoption Rate in Clinical Practice Around the World?","authors":"Konstantinos Z Vasileiou, George P Patrinos","doi":"10.1089/omi.2024.0049","DOIUrl":"10.1089/omi.2024.0049","url":null,"abstract":"","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855634","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":"Pancreatic Cancer and Longitudinal Multiomics Monitoring.","authors":"Vural Özdemir","doi":"10.1089/omi.2024.0058","DOIUrl":"10.1089/omi.2024.0058","url":null,"abstract":"","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868381","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":"Riddling Substitution of \"hsa\" to \"has\" in the Enigmatic MicroRNA Nomenclature.","authors":"Riya Vishwakarma, Krishnapriya Ramakrishnan, Niyas Rehman","doi":"10.1089/omi.2023.0248","DOIUrl":"10.1089/omi.2023.0248","url":null,"abstract":"<p><p>This concise review and analysis offers an initial unpacking of a previously under-recognized issue within the microRNA research and communications field regarding the inadvertent use of \"has\" instead of \"hsa\" in article titles in the microRNA nomenclature. This subtle change, often the result of grammar auto correction tools, introduces considerable ambiguity and confusion among readers and researchers in reporting of microRNA-related discoveries. The impact of this issue cannot be underestimated, as precise and consistent nomenclature is vital for science communication and computational retrieval of relevant scientific literature and to advance science and innovation. We suggest that the recognition and correction of these often inadvertent \"hsa\" to \"has\" substitution errors are timely and important so as to ensure a higher level of accuracy throughout the writing and publication process in the microRNA field in particular. Doing so will also contribute to clarity and consistency in the field of microRNA research, ultimately improving scientific veracity, communication, and progress.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859176","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":"Unpacking Immune Modulation as a Site of Therapeutics Innovation for Nematode Parasite <i>Wuchereria bancrofti</i>: A Temporal Quantitative Phosphoproteomics Profiling of Macrophage Migration Inhibitory Factor 2.","authors":"Ishwar Singh, Anagha Kanichery, Chinmaya Narayana Kotimoole, Prashant Kumar Modi, Thottethodi Subrahmanya Keshava Prasad, Sugeerappa Laxamannappa Hoti","doi":"10.1089/omi.2024.0002","DOIUrl":"10.1089/omi.2024.0002","url":null,"abstract":"<p><p>Nematode infections are common in both humans and livestock, with major adverse planetary health and economic impacts. <i>Wuchereria bancrofti</i> is a parasitic nematode that causes lymphatic filariasis, a neglected tropical disease that can lead to severe disability and deformity worldwide. For the long-term survival of the bancroftian parasites in the host, a complex immune invasion strategy is involved through immunomodulation. Therefore, immunomodulation can serve as a site of research and innovation for molecular targets. Macrophage migration inhibitory factor (<i>MIF</i>) is a pleiotropic cytokine crucial to the host antimicrobial alarm system and stress response. Interestingly, the nematode parasite <i>W. bancrofti</i> also produces two homologs of <i>MIF</i> (Wba-MIF1 and 2). Using a mass spectrometry-based phosphoproteomics approach, we report new findings on the immunomodulatory effect and signaling mechanism of Wba-MIF2 in macrophage cells. Accordingly, we observed 1201 phosphorylated sites on 467 proteins. Out of the 1201 phosphorylated sites, 1075, 117, and 9 were found on serine (S), threonine (T), and tyrosine (Y) residues, respectively. Our bioinformatics analysis led to identification of major pathways, including spliceosomes, T cell receptor signaling pathway, Th17 differentiation pathway, interleukin-17 signaling pathway, and insulin signaling pathway upon Wba-MIF2 treatment. Wba-MIF2 treatment also enriched <i>CDK4</i>, <i>CDK1</i>, and <i>DNAPK</i> kinases. The comparison of the signaling pathway of Wba-MIF2 with that of human-MIF suggests both share similar signaling pathways. These findings collectively offer new insights into the role and mechanism of Wba-MIF2 as an immunomodulator and inform future diagnostics and drug discovery research for <i>W. bancrofti</i>.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288656","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":"Deciphering Breast Cancer Metastasis Cascade: A Systems Biology Approach Integrating Transcriptome and Interactome Insights for Target Discovery.","authors":"Bikashita Kalita, Mohane Selvaraj Coumar","doi":"10.1089/omi.2023.0285","DOIUrl":"10.1089/omi.2023.0285","url":null,"abstract":"<p><p>Breast cancer is the lead cause of cancer-related deaths among women globally. Breast cancer metastasis is a complex and still inadequately understood process and a key dimension of mortality attendant to breast cancer. This study reports dysregulated genes across metastatic stages and tissues, shedding light on their molecular interplay in disease pathogenesis and new possibilities for drug discovery. Comprehensive analyses of gene expression data from primary breast tumor, circulating tumor cells, and distant metastatic sites in the brain, lung, liver, and bone were conducted. Genes dysregulated across multiple stages and tissues were identified as metastatic cascade genes, and are further classified based on functional associations with metastasis-related mechanisms. Their interactions with HUB genes in interactome networks were scrutinized, followed by pathway enrichment analysis. Validation for their potential as targets included assessments for survival, druggability, prognostic marker status, secretome annotation, protein expression, and cell type marker association. Results displayed critical genes in the metastatic cascade and those specific to metastatic sites, revealing the involvement of the collagen degradation and assembly of collagen fibrils and other multimeric structure pathways in driving metastasis. Notably, pivotal cascade genes <i>FABP4, CXCL12, APOD,</i> and <i>IGF1</i> emerged with high metastatic potential, linked to significant druggability and survival scores, establishing them as potential molecular targets. The significance of this research lies in its potential to uncover novel biomarkers for early detection, therapeutic targets, and a deeper understanding of the molecular mechanisms underpinning the metastatic cascade in breast cancer, and with an eye to precision/personalized medicine.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132253","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":"What Powers Trastuzumab's Cardiotoxicity? Decoding Mitochondrial-Related Gene Expression Through Integrative Review and Meta-Analysis in Cardiomyocytes.","authors":"Karoline Dos Santos Rodrigues, Daniel Sturza Lucas Caetano, João Vitor Cavalcante, Rodrigo Dalmolin, Patrícia K Ziegelmann, Michael Andrades","doi":"10.1089/omi.2024.0004","DOIUrl":"10.1089/omi.2024.0004","url":null,"abstract":"<p><p>Trastuzumab is a monoclonal antibody used in oncotherapy for HER2-positive tumors. However, as an adverse effect, trastuzumab elevates the risk of heart failure, implying the involvement of energy production and mitochondrial processes. Past studies with transcriptome analysis have offered insights on pathways related to trastuzumab safety and toxicity but limited study sizes hinder conclusive findings. Therefore, we meta-analyzed mitochondria-related gene expression data in trastuzumab-treated cardiomyocytes. We searched the transcriptome databases for trastuzumab-treated cardiomyocytes in the ArrayExpress, DDBJ Omics Archive, Gene Expression Omnibus, Google Scholar, PubMed, and Web of Science repositories. A subset of 1270 genes related to mitochondrial functions (biogenesis, organization, mitophagy, and autophagy) was selected from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology Resource databases to conduct the present meta-analysis using the Metagen package (Study register at PROSPERO: CRD42021270645). Three datasets met the inclusion criteria and 1243 genes were meta-analyzed. We observed 69 upregulated genes after trastuzumab treatment which were related mainly to autophagy (28 genes) and mitochondrial organization (28 genes). We also found 37 downregulated genes which were related mainly to mitochondrial biogenesis (11 genes) and mitochondrial organization (24 genes). The present meta-analysis indicates that trastuzumab therapy causes an unbalance in mitochondrial functions, which could, in part, help explain the development of heart failure and yields a list of potential molecular targets. These findings contribute to our understanding of the molecular mechanisms underlying the cardiotoxic effects of trastuzumab and may have implications for the development of targeted therapies to mitigate such effects.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102087","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":"Tyr352 as a Predominant Phosphosite in the Understudied Kinase and Molecular Target, HIPK1: Implications for Cancer Therapy.","authors":"Diya Sanjeev, Mejo George, Levin John, Athira Perunelly Gopalakrishnan, Pahal Priyanka, Spoorthi Mendon, Tanuja Yandigeri, Mahammad Nisar, Muhammad Nisar, Saptami Kanekar, Rex Devasahayam Arokia Balaya, Rajesh Raju","doi":"10.1089/omi.2023.0244","DOIUrl":"10.1089/omi.2023.0244","url":null,"abstract":"<p><p>Homeodomain-interacting protein kinase 1 (HIPK1) is majorly found in the nucleoplasm. HIPK1 is associated with cell proliferation, tumor necrosis factor-mediated cellular apoptosis, transcription regulation, and DNA damage response, and thought to play significant roles in health and common diseases such as cancer. Despite this, HIPK1 remains an understudied molecular target. In the present study, based on a systematic screening and mapping approach, we assembled 424 qualitative and 44 quantitative phosphoproteome datasets with 15 phosphosites in HIPK1 reported across multiple studies. These HIPK1 phosphosites were not currently attributed to any functions. Among them, Tyr352 within the kinase domain was identified as the predominant phosphosite modulated in 22 differential datasets. To analyze the functional association of HIPK1 Tyr352, we first employed a stringent criterion to derive its positively and negatively correlated protein phosphosites. Subsequently, we categorized the correlated phosphosites in known interactors, known/predicted kinases, and substrates of HIPK1, for their prioritized validation. Bioinformatics analysis identified their significant association with biological processes such as the regulation of RNA splicing, DNA-templated transcription, and cellular metabolic processes. HIPK1 Tyr352 was also identified to be upregulated in Her2+ cell lines and a subset of pancreatic and cholangiocarcinoma tissues. These data and the systems biology approach undertaken in the present study serve as a platform to explore the functional role of other phosphosites in HIPK1, and by extension, inform cancer drug discovery and oncotherapy innovation. In all, this study highlights the comprehensive phosphosite map of HIPK1 kinase and the first of its kind phosphosite-centric analysis of HIPK1 kinase based on global-level phosphoproteomics datasets derived from human cellular differential experiments across distinct experimental conditions.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143889","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":"Prediction of Essential Proteins of <i>Klebsiella pneumoniae</i> using Integrative Bioinformatics and Systems Biology Approach: Unveiling New Avenues for Drug Discovery.","authors":"Gnanasekar Pranavathiyani, Archana Pan","doi":"10.1089/omi.2024.0001","DOIUrl":"10.1089/omi.2024.0001","url":null,"abstract":"<p><p><i>Klebsiella pneumoniae</i> is an opportunistic multidrug-resistant bacterial pathogen responsible for various health care-associated infections. The prediction of proteins that are essential for the survival of bacterial pathogens can greatly facilitate the drug development and discovery pipeline toward target identification. To this end, the present study reports a comprehensive computational approach integrating bioinformatics and systems biology-based methods to identify essential proteins of <i>K. pneumoniae</i> involved in vital processes. From the proteome of this pathogen, we predicted a total of 854 essential proteins based on sequence, protein-protein interaction (PPI) and genome-scale metabolic model methods. These predicted essential proteins are involved in vital processes for cellular regulation such as translation, metabolism, and biosynthesis of essential factors, among others. Cluster analysis of the PPI network revealed the highly connected modules involved in the basic functionality of the organism. Further, the predicted consensus set of essential proteins of <i>K. pneumoniae</i> was evaluated by comparing them with existing resources (NetGenes and PATHOgenex) and literature. The findings of this study offer guidance toward understanding cell functionality, thereby facilitating the understanding of pathogen systems and providing a way forward to shortlist potential therapeutic candidates for developing novel antimicrobial agents against <i>K. pneumoniae</i>. In addition, the research strategy presented herein is a fusion of sequence and systems biology-based approaches that offers prospects as a model to predict essential proteins for other pathogens.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120227","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":"Multitarget Potential Drug Candidates for High-Grade Gliomas Identified by Multiple Reaction Monitoring Coupled with <i>In Silico</i> Drug Repurposing.","authors":"Ayushi Verma, Rushda Patel, Atharva Mahale, Rujuta Vijay Thorat, Soumya Lipsa Rath, Epari Sridhar, Aliasgar Moiyadi, Sanjeeva Srivastava","doi":"10.1089/omi.2023.0256","DOIUrl":"10.1089/omi.2023.0256","url":null,"abstract":"<p><p>High-grade gliomas (HGGs) are extremely aggressive primary brain tumors with high mortality rates. Despite notable progress achieved by clinical research and biomarkers emerging from proteomics studies, efficacious drugs and therapeutic targets are limited. This study used targeted proteomics, <i>in silico</i> molecular docking, and simulation-based drug repurposing to identify potential drug candidates for HGGs. Importantly, we performed multiple reaction monitoring (MRM) on differentially expressed proteins with putative roles in the development and progression of HGGs based on our previous work and the published literature. Furthermore, <i>in silico</i> molecular docking-based drug repurposing was performed with a customized library of FDA-approved drugs to identify multitarget-directed ligands. The top drug candidates such as Pazopanib, Icotinib, Entrectinib, Regorafenib, and Cabozantinib were explored for their drug-likeness properties using the SwissADME. Pazopanib exhibited binding affinities with a maximum number of proteins and was considered for molecular dynamic simulations and cell toxicity assays. HGG cell lines showed enhanced cytotoxicity and cell proliferation inhibition with Pazopanib and Temozolomide combinatorial treatment compared to Temozolomide alone. To the best of our knowledge, this is the first study combining MRM with molecular docking and simulation-based drug repurposing to identify potential drug candidates for HGG. While the present study identified five multitarget-directed potential drug candidates, future clinical studies in larger cohorts are crucial to evaluate the efficacy of these molecular candidates. The research strategy and methodology used in the present study offer new avenues for innovation in drug discovery and development which may prove useful, particularly for cancers with low cure rates.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697971","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":"Profiling Kinase Activities for Precision Oncology in Diffuse Gastric Cancer.","authors":"Smrita Singh, K T Shreya Parthasarathi, Mohd Younis Bhat, Champaka Gopal, Jyoti Sharma, Akhilesh Pandey","doi":"10.1089/omi.2023.0173","DOIUrl":"10.1089/omi.2023.0173","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a leading cause of cancer-related mortality globally. This is due to the fact that majority of the cases of GC are diagnosed at an advanced stage when the treatment options are limited and prognosis is poor. The diffuse subtype of gastric cancer (DGC) under Lauren's classification is more aggressive and usually occurs in younger patients than the intestinal subtype. The concept of personalized medicine is leading to the identification of multiple biomarkers in a large variety of cancers using different combinations of omics technologies. Proteomic changes including post-translational modifications are crucial in oncogenesis. We analyzed the phosphoproteome of DGC by using paired fresh frozen tumor and adjacent normal tissue from five patients diagnosed with DGC. We found proteins involved in the epithelial-to-mesenchymal transition (EMT), c-MYC pathway, and semaphorin pathways to be differentially phosphorylated in DGC tissues. We identified three kinases, namely, bromodomain adjacent to the zinc finger domain 1B (<i>BAZ1B</i>), <i>WNK</i> lysine-deficient protein kinase 1 (<i>WNK1</i>), and myosin light-chain kinase (<i>MLCK</i>) to be hyperphosphorylated, and one kinase, AP2-associated protein kinase 1 (<i>AAK1</i>), to be hypophosphorylated. <i>LMNA</i> hyperphosphorylation at serine 392 (S392) was demonstrated in DGC using immunohistochemistry. Importantly, we have detected heparin-binding growth factor (<i>HDGF</i>), heat shock protein 90 (<i>HSP90</i>), and <i>FTH1</i> as potential therapeutic targets in DGC, as drugs targeting these proteins are currently under investigation in clinical trials. Although these new findings need to be replicated in larger study samples, they advance our understanding of signaling alterations in DGC, which could lead to potentially novel actionable targets in GC.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564530","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}