{"title":"A 19-Gene Signature of Serous Ovarian Cancer Identified by Machine Learning and Systems Biology: Prospects for Diagnostics and Personalized Medicine.","authors":"Medi Kori, Talip Yasir Demirtas, Betul Comertpay, Kazim Yalcin Arga, Raghu Sinha, Esra Gov","doi":"10.1089/omi.2023.0273","DOIUrl":"10.1089/omi.2023.0273","url":null,"abstract":"<p><p>Ovarian cancer is a major cause of cancer deaths among women. Early diagnosis and precision/personalized medicine are essential to reduce mortality and morbidity of ovarian cancer, as with new molecular targets to accelerate drug discovery. We report here an integrated systems biology and machine learning (ML) approach based on the differential coexpression analysis to identify candidate systems biomarkers (i.e., gene modules) for serous ovarian cancer. Accordingly, four independent transcriptome datasets were statistically analyzed independently and common differentially expressed genes (DEGs) were identified. Using these DEGs, coexpressed gene pairs were unraveled. Subsequently, differential coexpression networks between the coexpressed gene pairs were reconstructed so as to identify the differentially coexpressed gene modules. Based on the established criteria, \"SOV-module\" was identified as being significant, consisting of 19 genes. Using independent datasets, the diagnostic capacity of the SOV-module was evaluated using principal component analysis (PCA) and ML techniques. PCA showed a sensitivity and specificity of 96.7% and 100%, respectively, and ML analysis showed an accuracy of up to 100% in distinguishing phenotypes in the present study sample. The prognostic capacity of the SOV-module was evaluated using survival and ML analyses. We found that the SOV-module's performance for prognostics was significant (<i>p</i>-value = 1.36 × 10<sup>-4</sup>) with an accuracy of 63% in discriminating between survival and death using ML techniques. In summary, the reported genomic systems biomarker candidate offers promise for personalized medicine in diagnosis and prognosis of serous ovarian cancer and warrants further experimental and translational clinical studies.</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":"139697970","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}
Aruldoss Immanuel, Ragothaman M Yennamalli, Venkatasubramanian Ulaganathan
{"title":"Targeting the Bottlenecks in Levan Biosynthesis Pathway in <i>Bacillus subtilis</i> and Strain Optimization by Computational Modeling and Omics Integration.","authors":"Aruldoss Immanuel, Ragothaman M Yennamalli, Venkatasubramanian Ulaganathan","doi":"10.1089/omi.2023.0277","DOIUrl":"10.1089/omi.2023.0277","url":null,"abstract":"<p><p>Levan is a fructan polymer with many industrial applications such as the formulation of hydrogels, drug delivery, and wound healing, among others. To this end, metabolic systems engineering is a valuable method to improve the yield of a specific metabolite in a wide range of bacterial and eukaryotic organisms. In this study, we report a systems biology approach integrating genomics data for the <i>Bacillus subtilis</i> model, wherein the metabolic pathway for levan biosynthesis is unpacked. We analyzed a revised genome-scale enzyme-constrained metabolic model (ecGEM) and performed simulations to increase levan biopolymer production capacity in <i>B. subtilis</i>. We used the model ec_iYO844_lvn to (1) identify the essential genes and bottlenecks in levan production, and (2) specifically design an engineered <i>B. subtilis</i> strain capable of producing higher levan yields. The FBA and FVA analysis showed the maximal growth rate of the organism up to 0.624 hr<sup>-1</sup> at 20 mmol gDw<sup>-1</sup> hr<sup>-1</sup> of sucrose intake. Gene knockout analyses were performed to identify gene knockout targets to increase the levan flux in <i>B. subtilis</i>. Importantly, we found that the <i>pgk</i> and <i>ctaD</i> genes are the two target genes for the knockout. The perturbation of these two genes has flux gains for levan production reactions with 1.3- and 1.4-fold the relative flux span in the mutant strains, respectively, compared to the wild type. In all, this work identifies the bottlenecks in the production of levan and possible ways to overcome them. Our results provide deeper insights on the bacterium's physiology and new avenues for strain engineering.</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":"139692535","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":"Technological Encounters in a Knowledge Economy: An Epistemic X-Ray.","authors":"Vural Özdemir","doi":"10.1089/omi.2024.0003","DOIUrl":"10.1089/omi.2024.0003","url":null,"abstract":"<p><p>Climate emergency is a planetary health and systems science challenge because human health, nonhuman animal health, and the health of the planetary ecosystems are coproduced and interdependent. Yet, we live in a time when climate emergency is tackled by platitudes and weak reforms instead of structural and systems changes, and with tools of the very same systems and metanarratives, for example, infinite growth at all costs, that are causing climate change in the first place. Seeking solutions to problems from within the knowledge frames and metanarratives that are causing the problems reproduces the same problems across time and geographies. This article examines and underlines the importance of an epistemological gaze on knowledge economy, an epistemological X-ray, as another solution in the toolbox of decolonial and other social justice struggles in an era of climate emergency. Epistemology questions and excavates the metanarratives embedded in knowledge forms that are popular, dominant, and hegemonic as well as knowledges that are silent, omitted, or erased. In this sense, epistemology does not take the \"archives\" of data and knowledge for granted but asks questions such as who, when, how, and with what and whose funding the archive was built, and what is included and left out? Epistemological choices made by innovators, funders, and knowledge actors often remain opaque in knowledge economies. Epistemology research is crucial for science and innovations to be responsive to planetary society and climate emergency and mindful of the social, political, neocolonial, and historical contexts of science and technology in the 21st century.</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":"139571196","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":"Cisplatin and Procaterol Combination in Gastric Cancer? Targeting Checkpoint Kinase 1 for Cancer Drug Discovery and Repurposing by an Integrated Computational and Experimental Approach.","authors":"Suchitha Giridhara Prema, Jaikanth Chandrasekaran, Saptami Kanekar, Mejo George, Thottethodi Subrahmanya Keshava Prasad, Rajesh Raju, Shobha Dagamajalu, Rex Devasahayam Arokia Balaya","doi":"10.1089/omi.2023.0163","DOIUrl":"10.1089/omi.2023.0163","url":null,"abstract":"<p><p>Checkpoint kinase 1 (CHK1), a serine/threonine kinase, plays a crucial role in cell cycle arrest and is a promising therapeutic target for drug development against cancers. CHK1 coordinates cell cycle checkpoints in response to DNA damage, facilitating repair of single-strand breaks, and maintains the genome integrity in response to replication stress. In this study, we employed an integrated computational and experimental approach to drug discovery and repurposing, aiming to identify a potent CHK1 inhibitor among existing drugs. An e-pharmacophore model was developed based on the three-dimensional crystal structure of the CHK1 protein in complex with CCT245737. This model, characterized by seven key molecular features, guided the screening of a library of drugs through molecular docking. The top 10% of scored ligands were further examined, with procaterol emerging as the leading candidate. Procaterol demonstrated interaction patterns with the CHK1 active site similar to CHK1 inhibitor (CCT245737), as shown by molecular dynamics analysis. Subsequent <i>in vitro</i> assays, including cell proliferation, colony formation, and cell cycle analysis, were conducted on gastric adenocarcinoma cells treated with procaterol, both as a monotherapy and in combination with cisplatin. Procaterol, in synergy with cisplatin, significantly inhibited cell growth, suggesting a potentiated therapeutic effect. Thus, we propose the combined application of cisplatin and procaterol as a novel potential therapeutic strategy against human gastric cancer. The findings also highlight the relevance of CHK1 kinase as a drug target for enhancing the sensitivity of cytotoxic agents in cancer.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403907","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":"Epstein-Barr Virus: Human Interactome Reveals New Molecular Insights into Viral Pathogenesis for Potential Therapeutics and Antiviral Drug Discovery.","authors":"Deepak Krishnan, Sreeranjini Babu, Rajesh Raju, Mohanan Valiya Veettil, Thottethodi Subramanya Keshava Prasad, Chandran S Abhinand","doi":"10.1089/omi.2023.0241","DOIUrl":"10.1089/omi.2023.0241","url":null,"abstract":"<p><p>Host-virus Protein-Protein Interactions (PPIs) play pivotal roles in biological processes crucial for viral pathogenesis and by extension, inform antiviral drug discovery and therapeutics innovations. Despite efforts to develop the Epstein-Barr virus (EBV)-host PPI network, there remain significant knowledge gaps and a limited number of interacting human proteins deciphered. Furthermore, understanding the dynamics of the EBV-host PPI network in the distinct lytic and latent viral stages remains elusive. In this study, we report a comprehensive map of the EBV-human protein interactions, encompassing 1752 human and 61 EBV proteins by integrating data from the public repository HPIDB (v3.0) as well as curated high-throughput proteomic data from the literature. To address the stage-specific nature of EBV infection, we generated two detailed subset networks representing the latent and lytic stages, comprising 747 and 481 human proteins, respectively. Functional and pathway enrichment analysis of these subsets uncovered the profound impact of EBV proteins on cancer. The identification of highly connected proteins and the characterization of intrinsically disordered and cancer-related proteins provide valuable insights into potential therapeutic targets. Moreover, the exploration of drug-protein interactions revealed notable associations between hub proteins and anticancer drugs, offering novel perspectives for controlling EBV pathogenesis. This study represents, to the best of our knowledge, the first comprehensive investigation of the two distinct stages of EBV infection using high-throughput datasets. This makes a contribution to our understanding of EBV-host interactions and provides a foundation for future drug discovery and therapeutic interventions.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378039","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":"Taking Political Determinants of Planetary Health Seriously: Expanding from P4 to P5 Medicine.","authors":"Vural Özdemir","doi":"10.1089/omi.2023.0276","DOIUrl":"10.1089/omi.2023.0276","url":null,"abstract":"<p><p>Predictive, Personalized, Preventive, and Participatory (P4) Medicine is embedded in the precision medicine conceptual framework to achieve the overarching goal of \"the right drug, for the right patient, at the right dose, and at the right time.\" Science cultures and political determinants of health have normative and instrumental impacts on P4 medicine. Yet, since the age of Enlightenment in the 17th century, science and economics have been disarticulated from politics along the lines of classical liberalism, and with an ahistorical approach that continues into the 21st century. The consequence of this liberal disarticulation is that science is falsely and narrowly understood as an invariably technocratic and objective field. In the aftermath of the Covid-19 pandemic, it is clearer that political determinants of health are the causes-of-causes for disease and health. I propose that we need P5 medicine with a fifth P, political determinants of planetary health. The new \"P\" can engage not only with instrumental aspects of P4 medicine research and clinical implementation but also with the structural factors that are an integral part of the politics of the P4 medicine. For example, the living legacies of colonialism contribute to the unequal relationships in trade, labor, provision, and production of materials among nation-states and between the Global South and the Global North and shape the class struggles in contemporary society, science, and medicine. A decolonial politics of care in which the political determinants of planetary health are taken seriously is therefore crucial and relevant to building a robust, ethical, responsible, and just P5 medicine in the 21st century.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049104","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}
Sakshi Rajoria, Sai Rohith Kavuru, Hari Sundar Pyda, Surbhi Bihani, Dhanush Borishetty, Deeptrup Biswas, Jeel Prajapati, Harshith Paladi, Sanjeeva Srivastava
{"title":"CoVProt: Toward a Mass Spectrometry Data Portal for COVID-19 Proteomics Research and Development.","authors":"Sakshi Rajoria, Sai Rohith Kavuru, Hari Sundar Pyda, Surbhi Bihani, Dhanush Borishetty, Deeptrup Biswas, Jeel Prajapati, Harshith Paladi, Sanjeeva Srivastava","doi":"10.1089/omi.2023.0274","DOIUrl":"10.1089/omi.2023.0274","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic has wreaked havoc globally. Beyond the pandemic, the long-term effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in multiple organ systems are yet to be deciphered. This calls for continued systems science research. Moreover, the host response to SARS-CoV-2 varies person-to-person and gives rise to different degrees of morbidity and mortality. Mass spectrometry (MS) has been a proven asset in studies of the SARS-CoV-2 from an omics systems science lens. To strengthen the proteomics research dedicated to COVID-19, we introduce here a web-based portal, CoVProt. The portal is work in progress and aims for a comprehensive curation of MS-based proteomics data of COVID-19 clinical samples for deep proteomic investigations, data visualization, and easy data accessibility for life sciences innovations and planetary health research community. Currently, CoVProt contains information on 2725 different proteins and 37,125 different peptides from six data sets covering a total of 202 clinical samples. Moreover, all pertinent data sets extracted from the literature have been reanalyzed using a common analysis pipeline developed by combining multiple tools. Going forward, we anticipate that the CoVProt portal will also provide access to the clinical parameters of the patients. The CoVProt (v1.0) portal addresses an existing significant gap to study COVID-19 host proteomics, which, to the best of our knowledge, is the first effort in this direction. We believe that CoVProt is poised to make contributions as a community resource for proteomic applications and aims to broadly support clinical studies to facilitate the discovery of COVID-19 biomarkers and therapeutics with translational potential.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403908","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":"Pharmacomicrobiomics-Guided Precision Oncology: A New Frontier of P4 (Predictive, Personalized, Preventive, and Participatory) Medicine and Microbiome-Based Therapeutics.","authors":"Kazim Yalcin Arga, Heba Attia, Ramy K Aziz","doi":"10.1089/omi.2023.0254","DOIUrl":"10.1089/omi.2023.0254","url":null,"abstract":"<p><p>Pharmacomicrobiomics is a rapidly developing field that promises to make significant contributions to predictive, personalized, preventive, and participatory (P4) medicine. This is becoming evident particularly in the field of precision (P4) oncology by taking seriously the crucial role microbiome plays in health and disease. Several studies have already shown that clinicians can harness insights from the microbiome to better predict treatment response, reduce side effects, and improve overall outcomes for cancer patients. Furthermore, pharmacomicrobiomics will undoubtedly play a crucial role in shaping the future of cancer treatment in the era of P4 oncology as we continue to unravel the intricate relationships between the microbiome and cancer. This perspective and innovation analysis discusses the emerging intersection of P4 medicine and P4 oncology, as seen through a lens of pharmacomicrobiomics. A key promise of pharmacomicrobiomics is the development of personalized microbiome-based therapeutics. In all, we suggest that optimizing cancer treatment and prevention by harnessing pharmacomicrobiomics has vast potentials for precision oncology, and personalized medicine using the right drug, at the right dose, for the right patient, and at the right time.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403909","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":"One Health Lens for Antimicrobial Resistance Research and Funding: A Systematic Review.","authors":"Issam Alsamara, Lesley Ogilvie, Ralf Sudbrak, Angela Brand","doi":"10.1089/omi.2023.0049","DOIUrl":"10.1089/omi.2023.0049","url":null,"abstract":"<p><p>One Health (OH) offers conceptual and applied prospects to advance planetary health and integrative biology in the 21st century. For example, The World Health Organization (WHO) has declared antimicrobial resistance (AMR) one of humanity's top 10 health threats worldwide (AMR). The AMR research, as seen through the OH lens, recognizes the interdependence and the coproduction of the health of humans, nonhuman animals, and the environment (the OH triad). Moreover, research and development (R&D) is required to generate potential solutions to prevent, diagnose, and treat infections and control the spread and emergence of AMR. However, it is still unclear how well the OH approach is integrated into current AMR R&D. In this study, we present a systematic review on the OH funding landscape for cross-sectoral AMR R&D, and its alignment/gaps with the current global strategic agenda on AMR. A systematic literature review was conducted using public databases covering the period between January 2015 and May 2022. We included the studies and reviews on AMR encompassing more than one sector of the OH triad. Out of the 777 included studies, 475 (61%) encompassed the three OH sectors. A key finding of the present systematic review is that the environment was the most neglected sector in the OH triad. AMR surveillance, transmission, and interventions are the most commonly studied priority topics. In addition, both cross-sectoral AMR literature and investments have been increasing since 2017. The operational aspect of AMR is the most researched and funded area. However, certain priority topics in the strategic research and innovation agenda of the Joint Programming Initiative on AMR are underrepresented in OH AMR research, such as diagnosis and therapeutics. To the best of authors' knowledge, this is the first study that systematically reviews the cross-sectoral literature on AMR, classifies it, and aligns and contextualizes it in regard to the funding landscape of AMR. This systematic review identifies neglected areas in AMR R&D and could serve as critical information for policymaking so as to realize the objectives of the Global Action Plan on AMR. Going forward, more cross-sectoral AMR research and funding are needed. As integrative biology and omics systems science are poised to benefit from a rapprochement with the OH lens, the present article highlights the AMR research and funding landscapes.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680511","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":"Hepatitis B Virus Modulated Transcriptional Regulatory Map of Hepatic Cellular MicroRNAs.","authors":"Krishnapriya Ramakrishnan, Sreeranjini Babu, Vineetha Shaji, Sowmya Soman, Anila Leelamma, Niyas Rehman, Rajesh Raju","doi":"10.1089/omi.2023.0171","DOIUrl":"10.1089/omi.2023.0171","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) is an enveloped, hepatotropic, noncytopathic virus with a partially double-stranded DNA genome. It infects hepatocytes and is associated with progression to liver fibrosis and cirrhosis, culminating in hepatocellular carcinoma (HCC), accounting for 55% of total HCC cases. MicroRNAs (miRNAs) regulated by HBV play an important role in these pathologies. Mapping the miRNAs responsive to HBV and HBV-specific proteins, including HBV X protein (HBx) that harbor the majority of HBV-human protein interactions, could aid accelerate the diagnostics and therapeutics innovation against the infection and associated diseases. With this in mind, we used a unique annotation strategy whereby we first amassed 362 mature HBV responsive-human Differentially Expressed miRNAs (HBV-hDEmiRs). The core experimentally-validated messenger RNA targets of the HBV-hDEmiRs were mostly associated with viral infections and hepatic inflammation processes. Moreover, our annotation strategy enabled the characterization of HBx-dependent/independent HBV-hDEmiRs as a tool for evaluation of the impact of HBx as a therapeutic target. Bioinformatics analysis of the HBV-human protein-protein interactome revealed new insights into the transcriptional regulatory network of the HBV-hDEmiRs. We performed a comparative analysis of data on miRNAs gathered from HBV infected cell line studies and from tissue studies of fibrosis, cirrhosis, and HCC. Accordingly, we propose hsa-miR-15a-5p that is downregulated by multiple HBV proteins, including HBx, as a potential biomarker of HBV infection, and its progression to HCC. In all, this study underscores (1) the complexity of miRNA regulation in response to HBV infection and its progression into other liver pathologies and (2) provides a regulatory map of HBV-hDEmiRs and the underlying mechanisms modulating their expression through a cross talk between HBV viral proteins and human transcription factors.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807115","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}