Rasmita Mishra, Sreelakshmi S Kumar, T Sayamsmruti Panda, Soumendu Mahapatra, Punit Prasad
{"title":"Live biotherapeutics in cancer therapy.","authors":"Rasmita Mishra, Sreelakshmi S Kumar, T Sayamsmruti Panda, Soumendu Mahapatra, Punit Prasad","doi":"10.1016/bs.pmbts.2026.01.002","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.002","url":null,"abstract":"<p><p>Cancer poses a global challenge in diagnostics and therapeutics. Treatments like chemotherapy, radiotherapy, surgery, and immunotherapy have significantly decreased the fatality rate, but drug resistance, therapy side effects, and relapse remain as major concerns. Live biotherapeutics are microorganisms that can be developed as therapeutic agents to modulate cancer pathophysiology and aid in disease management. Live biotherapeutic products (LBPs) have the potential to suppress tumour growth, enhance the effectiveness of conventional therapies, and reduce treatment-related side effects. Dysbiosis in the gut and cancer-specific tissues is linked to cancers of the colon, stomach, pancreas, and liver. Live biotherapeutics aim either to re-establish microbial balance or to employ microbes directly as anticancer tools. Both native and engineered LBPs (bacteria and viruses) represent promising interventions that may form part of next-generation cancer treatment strategies. Their clinical application draws on the integration of microbiology, immunology, synthetic biology, and oncology. LBPs can be used to target cancer cells by delivering antitumour payloads such as immune modulators, toxins, exposing cancer antigens, and molecules for targeted killing. LBPs offer advantages such as reduced systemic toxicity, overcoming drug resistance, and synergy with chemo-, radio-, and immunotherapies. Despite challenges in safety, manufacturing, regulation, and personalization, advances in synthetic biology and omics are enabling precision approaches. Future innovations such as bacteriobots, biocontainment systems, and patient-specific microbiome integration highlight their potential as next-generation cancer therapeutics.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"361-403"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229517","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":"Fecal microbiota transplantation in liver diseases: Therapeutic potential and associated risks.","authors":"Jayeeta Bhowmick, Arka Bagchi","doi":"10.1016/bs.pmbts.2026.01.001","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.001","url":null,"abstract":"<p><p>Fecal microbiota transplantation (FMT) is a biologically coherent strategy to modulate the gut-liver axis by restoring ecosystem structure and function. This chapter synthesizes current evidence and practice of FMT in various liver disease conditions. In cirrhosis with recurrent hepatic encephalopathy (HE), randomized trials demonstrate adjunctive benefits of FMT, reducing recurrence and hospitalizations as well as improving cognition, with route flexibility (lower-GI infusions or oral capsules) and emerging microbiome predictors of response. In severe alcohol-associated hepatitis and ACLF, early single-center trials suggest fewer infections and short-term survival gains, warranting confirmation in multicenter, blinded studies for further outcomes. For MASLD/MASH, FMT consistently shifts intestinal permeability, bile-acid signatures, and hepatic transcriptomics, although it has not reliably improved MRI-PDFF or insulin resistance in unselected cohorts; future success likely requires phenotype enrichment and function-matched donors or defined consortia. Data in chronic hepatitis B remain exploratory, positioning FMT, if at all, as an adjunct to antivirals. Methods are standardized around rigorous donor screening, controlled manufacturing, indication-specific endpoints, and strain-resolved engraftment analytics linking mechanism to outcome. Refractory Clostridium difficile is the only FDA-approved indication of FMT. Use of FMT in hepatology use should remain protocolled and regulated. Priorities include precision donor matching, next-generation consortia, platform trials, and long-term safety registries.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"229-246"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229554","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":"Artificial Intelligence in the prediction of 3D chromatin structure and gene regulation.","authors":"Antoni Pietryga, Dariusz Plewczynski","doi":"10.1016/bs.pmbts.2026.01.018","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.018","url":null,"abstract":"<p><p>All human cells share the same DNA sequence, yet their functional diversity is largely determined by the three-dimensional (3D) organization of chromatin within the nucleus. This spatial architecture regulates gene accessibility and expression, linking linear genomic information to cellular function. Recent advances in chromosome conformation capture technologies, such as Hi-C, ChIA-PET or HiChIP, have revealed hierarchical chromatin structures including compartments, topologically associating domains (TADs) and loops. Traditional computational methods often struggle to model these complex patterns, but artificial intelligence (AI), particularly deep learning, has emerged as a powerful tool for predicting both gene regulation and 3D chromatin organization from sequence and epigenomic features. Integrative and multimodal approaches, extended by self-supervised models, enable accurate modeling of regulatory mechanisms across cell types, providing novel insights into genome function and the molecular basis of disease.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"221 ","pages":"125-144"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693349","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":"Artificial intelligence in microbial metagenomics.","authors":"Alisha Ansari, Omprakash Shete, Tarini Shankar Ghosh","doi":"10.1016/bs.pmbts.2026.01.009","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.009","url":null,"abstract":"<p><p>Rapid advancements in genomic sequencing technologies and similar technological advancements in the area of accessing, isolating, extracting and functional probing of microbes residing in diverse environments has resulted in a deluge of microbiome sequencing and microbial genomic sequencing data. Concomitant developments in the area of data science, specifically in the domains of advanced statistics, and artificial intelligence (AI) can facilitate mining this data to answer complex biological questions and developing translational applications in diverse areas, ranging from health-care to industrial microbiology. For most researchers, information on which AI tools address specific biological questions is scattered across disparate sources. In this chapter, we explore the various applications of AI-based methodologies (using case-studies) in answering different biological questions using microbial genomics and metagenomic data. We also discuss different AI and machine-learning (ML) based approaches to integrate metagenomic data with other \"omics\" data. Finally, we highlight both challenges and possibilities with this rapidly progressing field.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"221 ","pages":"255-276"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693404","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":"Recombinant live biotherapeutics: A new frontier in peptide drug biosynthesis and precision delivery.","authors":"Meenal Chawla, Omkar Bhange, Bhabatosh Das","doi":"10.1016/bs.pmbts.2025.12.002","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2025.12.002","url":null,"abstract":"<p><p>Peptide-based therapeutics are widely employed in the treatment and management of various medical conditions, including diabetes, obesity, cancer, rare diseases, and microbial infections. This chapter reviews the evolution of technologies used in peptide production including chemical synthesis, recombinant DNA technology, and other advanced methods that have driven significant progress in pharmaceutical development. However, the development of peptide therapeutics is challenged by issues related to high production costs, limited stability, delivery barriers, and potential toxicity. To overcome these issues, recombinant live biotherapeutics (rLBPs), can be utilized as live microbioreactor, where genetically engineered microorganisms are employed to produce and deliver therapeutic peptides directly within the host. Recombinant LBPs enable accurate, sustained, and targeted delivery of therapeutic peptides with enhanced safety, efficacy and cost-effective manufacturing. Furthermore, this chapter highlights the advancements of genetic engineering tools that have enabled the modification and development of rLBPs as microbioreactor, highlighting their emerging role and therapeutic potential in curing disorders.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"175-207"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229193","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":"AI-driven gene-sets, networks, pathways, and interactions analyses of multi-omics data.","authors":"Zongliang Yue, Zeru Zhang, Quanghuy Thanh, Thanh Nguyen, Zhandos Sembay, Hao Chen, Robert Welner, Jake Chen","doi":"10.1016/bs.pmbts.2026.01.023","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.023","url":null,"abstract":"<p><p>High-throughput omics technologies continue to expand the scale and dimensionality of biological datasets across research and clinical environments. Yet transforming these large molecular feature sets into mechanistic insight remains a central challenge in translational bioinformatics. Gene-set and pathway-based approaches address this need by providing biologically meaningful organizational units, such as processes, signaling modules, complexes, or phenotypic signatures, through which experimental signals can be interpreted. PAGER 3.0 represents a major advance in the PAGER knowledge ecosystem, offering an expanded and curated collection of Pathways, Annotated gene-lists and Gene signatures (PAGs), ontology-aware knowledge navigation, weighted enrichment analytics, and structured network-based prioritization tools. This chapter introduces the conceptual foundations of PAG-based analysis, details PAGER 3.0 architecture and analytical workflows, and demonstrates utility through a leukemia single-cell transcriptomics case study. Applications in systems biology, precision medicine, machine learning, and drug repurposing are also discussed.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"221 ","pages":"277-313"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693266","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":"Artificial Intelligence in single-cell and spatial transcriptomics data analyses.","authors":"Sangeeta Singh, Sonu Kumar, Dinesh Gupta","doi":"10.1016/bs.pmbts.2026.01.011","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.011","url":null,"abstract":"<p><p>Single-cell (SC) and spatial transcriptomics (ST) have transformed molecular biology by allowing high-resolution profiling of gene expression in individual cells and tissues. These approaches reveal cellular diversity, developmental pathways, and disease processes, yet the resulting datasets are large and complex. Artificial intelligence (AI) especially machine learning (ML) and deep learning (DL) now plays a central role in managing this complexity by automating preprocessing, reducing dimensionality, and supporting cell classification and clustering. AI methods also help integrate multi-omics layers, identify spatial patterns, and infer cellular trajectories, strengthening our ability to interpret biological systems. This chapter examines how AI advances the analysis of single-cell and spatial transcriptomics, focusing on methods such as convolutional neural networks (CNN), graph neural networks, (GNN) and variational autoencoders (VAE). It highlights applications in cancer biology, immunology, and neuroscience, including the prediction of cellular behavior and disease mechanisms relevant to personalized medicine. Remaining challenges include scalability, interpretability, and consistent data standards. The chapter concludes with future directions aimed at improving model transparency, enhancing multi-modal integration, and addressing ethical issues in clinical use, offering researchers a concise guide to applying AI for deeper insights into cellular data.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"221 ","pages":"99-124"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693367","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}
Love Kaushik, A T Vivek, Simran Arora, Fiza Hamid, Kanka Mukherjee, Niyati Bisht, Sakshi Chaudhary, Jagriti Shukla, Sakshi Nawani, Shailesh Kumar
{"title":"The Intersection of AI and genomics in health and disease: Advancements and applications.","authors":"Love Kaushik, A T Vivek, Simran Arora, Fiza Hamid, Kanka Mukherjee, Niyati Bisht, Sakshi Chaudhary, Jagriti Shukla, Sakshi Nawani, Shailesh Kumar","doi":"10.1016/bs.pmbts.2026.01.013","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.013","url":null,"abstract":"<p><p>AI and genomics are revolutionizing precision medicine by using machine learning (ML) to analyze large-scale next-generation sequencing (NGS) data, identifying genetic mutations and biomarkers for personalized therapies. In practice, this accelerates drug discovery and enhances variant detection, while in cancer genomics, AI enables early detection via liquid biopsies and refines treatment by integrating multi-omics data to improve therapeutic precision. However, challenges such as data biases in underrepresented populations, limited model interpretability, and ethical concerns regarding privacy and algorithmic inequity hinder clinical adoption and demand robust governance. Efforts to diversify datasets also face standardization hurdles, although explainable AI and federated learning provide promising solutions for improving transparency and privacy. In this chapter, we discuss the role of AI in advancing genomics from diagnostics to novel therapies and emphasize the need for equitable frameworks to ensure responsible implementation, thereby paving the way for breakthroughs in personalized medicine.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"221 ","pages":"71-97"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693372","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":"Recent advances of microbial medicine to prevent and treat cardiovascular disease.","authors":"Shriram Mahajan, Anagha Nk, Sanjay K Banerjee","doi":"10.1016/bs.pmbts.2026.01.028","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.028","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with standard pharmacological interventions often failing to fully address their complex pathophysiology. Recent advances in microbial medicine highlight the human gut microbiome as a critical regulator of cardiovascular health. Gut microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and indole derivatives play pivotal roles in modulating inflammation, lipid metabolism, immune function, and vascular homeostasis. Dysbiosis, or microbial imbalance, has been strongly associated with atherosclerosis, hypertension, and heart failure. Consequently, therapies targeting the gut microbiota including probiotics, prebiotics, synbiotics, and postbiotics have emerged as promising adjuncts in CVD prevention and treatment. Moreover, fecal microbiota transplantation (FMT) and synthetic biology approaches using engineered microbes offer novel strategies to restore microbial balance and deliver therapeutic molecules. Dietary interventions, particularly Mediterranean and fiber-rich diets, further support cardiovascular health through microbiota modulation. While preclinical and clinical studies underscore the potential of microbiome-based interventions, challenges related to strain specificity, delivery systems, and regulatory frameworks remain. Nonetheless, integrating microbial medicine into cardiovascular care represents a transformative shift toward precision, holistic, and personalized treatment paradigms. This chapter explores these cutting-edge therapeutic interventions and their implications for reshaping the future landscape of cardiovascular disease management.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"305-337"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228957","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":"Clinical applications of live biotherapeutics: Current trends and future prospects.","authors":"Dipasri Konar","doi":"10.1016/bs.pmbts.2026.01.003","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.003","url":null,"abstract":"<p><p>Live biotherapeutic (LBP) is defined by the FDA as a biological product that: (1) contains live organisms, such as bacteria; (2) applies to the prevention, treatment, or cure of a disease or condition of human beings; and (3) is not a vaccine. Progress in microbiome science and the limitations of antibiotics have necessitated the use of LBPs to complement or replace conventional therapies across multiple medical disciplines. The most important advancement is in the infectious disease domain, where fecal microbiota transplantation validated ecological restoration for recurrent Clostridioides difficile infection and paved the way for the first approved LBPs (REBYOTA® and VOWST™/SER-109). Constructing rational microbial consortia and strain-level strategies aim to induce commensal resilience and prevent the establishment of multidrug-resistant organisms. In oncology, gut microbial composition modulates response to immune checkpoint inhibitors. So, defined microbial consortia and engineered E. coli Nissle are being developed to enhance antitumor immunity and localize payloads. Early studies in animals and humans also support the application of this approach in metabolic disease, allergy, and oral health. Translation from benchside to bedside, however, is fraught with hurdles-variable patient response, manufacturing consistency, safety standards, cost, and ethics-exacerbated by heterogeneous global regulations, underscoring the need for harmonization. Precision microbial consortia, programmable \"living medicines,\" and biohybrid formulations could extend LBPs into broader indications and global health, shifting practice toward an ecological model of therapeutics.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"103-138"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229541","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}