Omics A Journal of Integrative Biology最新文献

The traditional way of thinking about human diseases across clinical and narrow phenomics silos often masks the underlying shared molecular substrates across human diseases. One Health and planetary health fields particularly address such complexities and invite us to think across the conventional disease nosologies. For example, tuberculosis (TB) and lung cancer (LC) are major pulmonary diseases with significant planetary health implications. Despite distinct etiologies, they can coexist in a given community or patient. This is both a challenge and an opportunity for preventive medicine, diagnostics, and therapeutics innovation. This study reports a bioinformatics analysis of publicly available gene expression data, identifying overlapping dysregulated genes, downstream regulators, and pathways in TB and LC. Analysis of NCBI-GEO datasets (GSE83456 and GSE103888) unveiled differential expression of CEACAM6, MUC1, ADM, DYSF, PLOD2, and GAS6 genes in both diseases, with pathway analysis indicating association with lysine degradation pathway. Random forest, a machine-learning-based classification, achieved accuracies of 84% for distinguishing TB from controls and 83% for discriminating LC from controls using these specific genes. Additionally, potential drug targets were identified, with molecular docking confirming the binding affinity of warfarin to GAS6. Taken together, the present study speaks of the pressing need to rethink clinical diagnostic categories of human diseases and that TB and LC might potentially share molecular substrates. Going forward, planetary health and One Health scholarship are poised to cultivate new ways of thinking about diseases not only across medicine and ecology but also across traditional diagnostic conventions.

Hepatitis B virus (HBV) infection has been causally linked to hepatocellular carcinoma (HCC) in more than 50% cases. MicroRNAs (miRNAs) play cross-cutting mechanistic roles in the complex interplay between viral pathogenesis, host survival, and clinical outcomes. The present study set out to identify etiologically significant human miRNAs associated with HBV infection in liver-related pathologies leading to HCC. In diverse tissue types, we assembled 573 miRNAs differentially expressed in HBV-associated liver pathologies, HBV infection, fibrosis, cirrhosis, acute on chronic liver failure, and HCC. Importantly, 43 human differentially expressed miRNAs (hDEmiRs) were regulated in serum/plasma and liver tissue of patients with HBV-positive conditions. However, only two hDEmiRs, hsa-miR-21-5p and hsa-miR-143-3p, were regulated across all disease conditions. To shortlist the functional miRNAs in HBV-induced HCC pathogenesis, a reverse bioinformatics analysis was performed using eight GEO datasets and the TCGA database containing the list of differentially regulated mRNAs in HCC. A comparative study using these data with the identified targets of hDEmiRs, a set of unidirectionally regulated hDEmiRs with the potential to modulate mRNAs in HCC, were found. Moreover, our study identified five miRNAs; hsa-miR-98-5p, hsa-miR-193b-3p, hsa-miR-142-5p, hsa-miR-522-5p, and hsa-miR-370-3p targeting PIGC, KNTC1, CSTF2, SLC41A2, and RAB17, respectively, in HCC. These hDEmiRs and their targets could be pivotal in HBV infection and subsequent liver pathologies modulating HCC clinical progression. HBV infection is the largest contributor to HCC, and the present study comprises the first of its kind compendium of hDEmiRs related to HBV-related pathologies.

A One Health lens is increasingly significant to address the intertwined challenges in planetary health concerned with the health of humans, nonhuman animals, plants, and ecosystems. A One Health approach can benefit the public health systems in Africa that are overburdened by noncommunicable, infectious, and environmental diseases. Notably, the COVID-19 pandemic revealed the previously overlooked two-fold importance of pharmacogenetics (PGx), for individually tailored treatment of noncommunicable diseases and environmental pathogens. For example, dyslipidemia, a common cardiometabolic risk factor, has been identified as an independent COVID-19 severity risk factor. Observational data suggest that patients with COVID-19 infection receiving lipid-lowering therapy may have better outcomes. However, among African patients, the response to these drugs varies from patient to patient, pointing to the possible contribution of genetic variation in important pharmacogenes. The PGx of lipid-lowering therapies may underlie differences in treatment responses observed among dyslipidemia patients as well as patients comorbid with COVID-19 and dyslipidemia. Genetic variations in APOE, ABCB1, CETP, CYP2C9, CYP3A4, CYP3A5, HMGCR, LDLR, NPC1L1, and SLCO1B1 genes affect the pharmacogenomics of statins, and they have individually been linked to differential responses to dyslipidemia and COVID-19 treatment. African populations are underrepresented in PGx research. This leads to poor accounting of additional diverse genetic variants that could be important in understanding interindividual and between-population variations in therapeutic responses to dyslipidemia and COVID-19. This expert review examines and synthesizes the salient and priority PGx variations, as seen through a One Health lens in Africa, to improve and inform personalized medicine in both dyslipidemia and COVID-19.

Food production must undergo systems change to meet the sustainable development goals (SDGs). For example, organic farming can be empowered by soil microorganisms with plant growth promotion (PGP) and biocontrol features. In this context, there have been limited studies on pomegranate. We investigated microbial diversity in rhizosphere of the pomegranate "Bhagwa" variety and its potential role in PGP and biocontrol. Both bulk and rhizosphere soil samples were analyzed for their physicochemical properties. Whole metagenome sequencing was conducted using the Illumina NovaSeq6000 platform. Surprisingly, we found that bulk and rhizosphere soil samples had comparable microbial diversity. Metagenome sequencing revealed the abundance of Streptomyces indicus, Bradyrhizobium kalamazoonesis, and Pseudomonas cellulosum in the rhizosphere that are reported here for the first time in agricultural literature. Pathway prediction analysis using KEGG (Kyoto Encyclopedia for Genes and Genomes) and COG (clusters of orthologous genes) databases identified metabolic pathways associated with biocontrol properties against pathogens. We confirmed the metagenome data in vitro, which demonstrated their PGP potential and antimicrobial properties. For instance, S. indicus produced high concentration of indole-3-acetic acid, a PGP phytohormone, that can stimulate plant growth. In addition, an antimicrobial susceptibility assay suggested that bacterial extracts displayed activity against Xanthomonas, a primary pathogen causing the pomegranate wilt disease. In conclusion, this study suggests that S. indicus, B. kalamazoonesis, and P. cellulosum can potentially be PGP and biocontrol agents that may contribute to increased crop productivity in pomegranate cultivation. These agents and their combinations warrant future research with an eye on SDGs and so as to enable and innovate organic farming and pomegranate agricultural practices.

A quiet quadruple revolution has been in the making in systems science with convergence of (1) artificial intelligence, machine learning, and other digital technologies; (2) multiomics big data integration; (3) growing interest in the "variability science" of precision/personalized medicine that aims to account for patient-to-patient and between-population differences in disease susceptibilities and responses to health interventions such as drugs, nutrition, vaccines, and radiation; and (4) planetary health scholarship that both scales up and integrates biological, clinical, and ecological contexts of health and disease. Against this overarching background, this article presents and highlights some of the salient challenges and prospects of multiomics research, emphasizing the attendant pivotal role of systems medicine and systems biology. In addition, we emphasize the rapidly growing importance of planetary health research for systems medicine, particularly amid climate emergency, ecological degradation, and loss of planetary biodiversity. Looking ahead, we anticipate that the integration and utilization of multiomics big data and artificial intelligence will drive further progress in systems medicine and systems biology, heralding a promising future for both human and planetary health.

The axolotl (Ambystoma mexicanum) is renowned for its remarkable regenerative capabilities, which are not diminished by the transition from a neotenic to a metamorphic state. This study explored the microbiome dynamics in axolotl limb regeneration by examining the microbial communities present in neotenic and metamorphic axolotls at two critical stages of limb regeneration: pre-amputation and during blastema formation. Utilizing 16S rRNA amplicon sequencing, we investigated the variations in microbiome profiles associated with different developmental and regenerative states. Our findings reveal a distinct separation in the microbiome profiles of neotenic and metamorphic samples, with a clear demarcation in microbial composition at both the phylum and genus levels. In neotenic 0DPA samples, Proteobacteria and Firmicutes were the most abundant, whereas in neotenic 7DPA samples, Proteobacteria and Bacteroidetes dominated. Conversely, metamorphic samples displayed a higher abundance of Firmicutes and Bacteroidetes at 0DPA and Proteobacteria and Firmicutes at 7DPA. Alpha and beta diversity analyses, along with dendrogram construction, demonstrated significant variations within and between the sample groups, suggesting a strong influence of both developmental stage and regenerative state on the microbiome. Notably, Flavobacterium and Undibacterium emerged as distinctive microbial entities in neotenic 7DPA samples, highlighting potential key players in the microbial ecology of regeneration. These findings suggest that the axolotl's microbiome is dynamically responsive to blastema formation, and they underscore the potential influence of microbial communities on the regeneration process. This study lays the groundwork for future research into the mechanisms by which the microbiome may modulate regenerative capacity.

MicroRNAs (miRNAs) have emerged as a prominent layer of regulation of gene expression. This article offers the salient and current aspects of machine learning (ML) tools and approaches from genome to phenome in miRNA research. First, we underline that the complexity in the analysis of miRNA function ranges from their modes of biogenesis to the target diversity in diverse biological conditions. Therefore, it is imperative to first ascertain the miRNA coding potential of genomes and understand the regulatory mechanisms of their expression. This knowledge enables the efficient classification of miRNA precursors and the identification of their mature forms and respective target genes. Second, and because one miRNA can target multiple mRNAs and vice versa, another challenge is the assessment of the miRNA-mRNA target interaction network. Furthermore, long-noncoding RNA (lncRNA)and circular RNAs (circRNAs) also contribute to this complexity. ML has been used to tackle these challenges at the high-dimensional data level. The present expert review covers more than 100 tools adopting various ML approaches pertaining to, for example, (1) miRNA promoter prediction, (2) precursor classification, (3) mature miRNA prediction, (4) miRNA target prediction, (5) miRNA- lncRNA and miRNA-circRNA interactions, (6) miRNA-mRNA expression profiling, (7) miRNA regulatory module detection, (8) miRNA-disease association, and (9) miRNA essentiality prediction. Taken together, we unpack, critically examine, and highlight the cutting-edge synergy of ML approaches and miRNA research so as to develop a dynamic and microlevel understanding of human health and diseases.

How we choose to respond to uncertainty matters for robust and responsible science. New laws and consensus reports are popular instruments for global governance of emerging technology and attendant uncertainty. However, the sociologist Pierre Bourdieu noted that "[t]he judicial situation operates like a neutral space that neutralizes the stakes in any conflict through the de-realization and distancing implicit in the conversion of a direct struggle between parties into a dialogue between mediators." Put in other words, while law and legal modes of reasoning are certainly useful for conflict resolution and closure, their overprivileging in emerging technology and uncertainty governance can potentially bring about depoliticization by transforming the struggles and dissent necessary for democratic governance into a "dialogue between mediators." Hence, the critical sociological gaze offered by Bourdieu is particularly relevant for democratization of global governance of multiomics technologies and timely with the current uptake of personalized medicine. For example, in May 2023, the Romanian government introduced a law to give patients the right to personalized medicine. Personalized medicine is related to the larger umbrella concept and field of theranostics, the fusion of therapeutics and diagnostics. It is therefore timely to reflect on a "right for theranostics in planetary health," considering the potential for future pandemics and ecological crises in the 21st century. Rather than forcing consensus or convergence in an innovation ecosystem, dissent grounded in rigorous political theory, sociology of law and critical legal studies can strengthen democratization and global governance for personalized medicine and multiomics technologies.

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research.

This analysis and commentary discuss Romania's landmark law, the first globally, acknowledging the right of citizens and patients to personalized medicine. Initiated following the EU Council's 2015 policy on personalized medicine, the law is a result of intersectoral collaborative efforts led by the Centre for Innovation in Medicine in Romania using a quadruple (later evolved to penta) helix model involving academia, public, private, and civil society sectors. Promulgated on May 24, 2023, the law legally entitles patients to personalized health care and in ways informed by individual genetic and phenotypic consideration. The law mandates informed consent for medical interventions and ensures data protection in accordance with the General Data Protection Regulation. We suggest that this pioneering legislation paves the way for integrating personalized medicine into Romania's health care system, shaping clinical practice, research, and health policy. In all, it marks a significant step in redefining health care delivery, emphasizing individualized treatment and the political determinants of personalized medicine, and setting a precedent for future health care innovations worldwide.