Omics A Journal of Integrative Biology最新文献

Microtubule-associated serine/threonine-protein kinase 3 (MAST3) is a member of the MAST kinase family implicated in neuronal and immune pathways and is predicted to associate with cytoskeletal regulation. However, insights into its functional role in cytoskeletal organization remain unexplored. In this study, we performed a large-scale phosphoproteomic analysis of MAST3 using 562 datasets to delineate its functional network. We identified four predominant phosphosites, S134, S146, S792, and S793, based on the frequency of detection and differential regulation, with S134 and S146 localized within the Domain of Unknown Function domain, a noncatalytic region. These phosphosites exhibited distinct coregulatory profiles, suggesting regulation through noncatalytic domains. Coregulated phosphosites were enriched for cytoskeleton-associated functions, including actin filament organization, microtubule organization, and spindle assembly. Additionally, predicted downstream substrates such as KIF15, EPB41L1, CP110, and HNRNPU, and binary interactors including LMNA, CKAP4, and CAMSAP2, further support the involvement of MAST3 in cytoskeletal regulation. The convergence of these cytoskeletal partners across phosphosites, substrates, and interactors suggests that MAST3 may act as a key modulator of cytoskeletal organization through phosphorylation-dependent protein-protein interactions. Notably, frequent phosphorylation of S146 across cancer types points to a potential tumor-specific regulatory role. Together, these findings provide the first systems-level insight into the role of MAST3 in cytoskeletal regulation and disease relevance.

The increasing accessibility of high-throughput omics technologies has represented a paradigm change in systems biology, facilitating the systematic exploration of biological complexity at genomic, transcriptomic, proteomic, and metabolomic levels. Contemporary systems biology more and more depends on integrative multi-omics strategies to unravel the sophisticated, dynamic networks of cellular function and organismal phenotypes. Such methodologies enable scientists to clarify molecular interactions, decipher disease pathology, identify strong biomarkers, and guide precision medicine and synthetic biology initiatives. Recent technological breakthroughs in computational tools, ranging from early or late data integration, network analysis, and machine learning, have overcome obstacles of high-dimensionality, heterogeneity, and perturbations restricted to specific contexts. In this review, we critically assess the principles, methods, and applications of multi-omics integration, with an emphasis on cancer biology, microbial engineering, and synthetic biology. We showcase case studies in which integrative omics provided actionable findings. Finally, we address current limitations (e.g., data heterogeneity, interpretability) and forthcoming solutions (artificial intelligence, single-cell omics, cloud platforms). By closing the gap between molecular layers, multi-omics integration is moving toward predictive models of biological systems and revolutionary biotechnological applications.

Lung adenocarcinoma (LUAD) remains the most common subtype of lung cancer, characterized by high heterogeneity and poor survival outcomes. Although transcriptomic and metabolomic alterations have been individually studied, integrated multi-omics analyses are needed to uncover the convergent pathways that drive tumor progression. Differentially expressed genes (DEGs) were identified from the GSE229253 transcriptomic dataset comprising LUAD tumor and adjacent normal tissues, while significantly altered metabolites were obtained from the Lung Cancer Metabolome Database. The top 10 DEGs and metabolites were analyzed using the search tool for interacting chemicals (STITCH) to construct gene-metabolite networks, and Integrated Molecular Pathway Level Analysis (IMPaLA) was employed for integrated pathway enrichment to identify overlapping molecular processes. Transcriptomic profiling revealed 973 DEGs (410 upregulated and 563 downregulated), and metabolomic analysis identified significant alterations in metabolites linked to redox balance, amino acid derivatives, and nucleotide metabolism. Integration through STITCH generated a network of 16 nodes and 9 edges, highlighting gene-metabolite associations of probable biological relevance. Joint pathway enrichment analysis using IMPaLA consistently identified glycosylation-related pathways, particularly O-linked glycosylation of mucins, as major axes of convergence between transcriptomic and metabolomic alterations in LUAD (joint p = 0.00129-0.00434). Several genes (B3GNT6, FEZF1-AS1, and LCAL1) and metabolites (isoleucylleucine, leucylleucine, and isoleucylvaline) are probable novel candidates, warranting further investigation. These findings provide systems-level evidence that aberrant glycosylation is likely a central hallmark of LUAD, underscore the potential of glycosylation pathways as biomarkers and therapeutic targets, and demonstrate the utility of cross-omics approaches to unpack the molecular complexity of lung cancer.

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and fatal interstitial lung disease (ILD) characterized by abnormal epithelial cell behavior and excessive extracellular matrix deposition. Despite advances in understanding its molecular pathogenesis, the lack of early diagnostic biomarkers and effective targeted therapies remains a critical barrier. Metabolomics is the comprehensive profiling of low-molecular-weight metabolites and offers an emerging lens to unpack the complex metabolic reprogramming in IPF. This expert review discusses (1) current metabolomics approaches used in IPF research and (2) the key dysregulated metabolic pathways and their potential in improving diagnosis, prognostication, and treatment response monitoring. Furthermore, the review outlines the key metabolic signatures identified in non-IPF ILDs as well and compares their roles with those observed in IPF, thereby providing a broader perspective on shared and disease-specific metabolic alterations across the ILD spectrum.

The classification of immune and nonimmune genes in cattle is crucial for understanding immune mechanisms and their link to disease resistance. Traditional methods rely on manual curation and conventional bioinformatics tools, which are often time-consuming and labor-intensive. We introduce ImmFinder, a multimodal fully connected neural network (FCNN) framework designed to classify immune genes by integrating genomic and transcriptomic datasets. ImmFinder achieved an accuracy of 85.67%, an F1-score of 0.85, a precision of 0.86, and a recall of 0.85, demonstrating strong predictive performance. Additionally, the area under the curve-receiver operating characteristic (AUC-ROC) curve scores of 0.9250 (test set) and 0.9264 (validation set) further validate its robustness. These findings highlight the potential of a multimodal deep learning approach for immune gene classification, advancing functional genomics in cattle. The limitations of ImmFinder include reliance on the available bovine genomic and transcriptomic datasets used for training and evaluation, which may constrain immediate generalization to other breeds or species; additional external validation and experimental follow-up will be required to confirm biological hypotheses derived from model predictions. Currently, ImmFinder demonstrates the value of multimodal data fusion for functional gene annotation and provides a scalable baseline for integrating data types, such as genomics and transcriptomics. In future work, we will expand the training cohorts, broaden the range of data modalities, and pursue experimental validation of high-confidence model predictions. ImmFinder is implemented in Python, and all datasets, training models, preprocessing, and model development scripts are available on GitHub.

Cancer is a disease with heterogenous molecular signatures that ought to be unpacked to achieve the overarching aim of precision oncology. A pan-cancer omics approach provides a systems science framework to explore shared and distinct mechanisms across cancers. We report here pan-cancer analyses of gene expression data from 17 cancers, for example, adrenocortical cancer, lung cancer, kidney cancer, and colorectal cancer, and 26 tissue types, using public datasets to construct disease-specific transcriptional networks. Using the hypergeometric test, 1005 microRNAs (miRNAs), 314 transcription factors (TFs), and 332 receptors were identified as regulatory molecules interacting with differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed to explore their functional roles. Accordingly, we found miR-124-3p, miR-6799-5p, and miR-7106-5p as common miRNAs; Specificity Protein 1 (SP1), RELA Proto-Oncogene, NF-κB Subunit (RELA), and Nuclear Factor Kappa B Subunit 1 (NFKB1) as shared TFs; Cyclin-Dependent Kinase 2 (CDK2), Histone Deacetylase 1 (HDAC1), and ABL Proto-Oncogene 1, Non-Receptor Tyrosine Kinase (ABL1) as common receptors; and pathways in cancer, PI3K-Akt signaling, and p53 signaling as commonly enriched. Survival analysis in an independent dataset confirmed these findings: SP1 and NFKB1 were significant in 9 cancers, RELA in 6, whereas CDK2, HDAC1, and ABL1 were significant in 11, 10, and 10 cancers, respectively, out of the 17 cancers researched herein. In conclusion, these findings provide system-level insights on tumor heterogeneity and inform future cancer classification, for example, according to shared and distinct molecular signatures and development of therapies that might prove effective across several cancers. We underline that unpacking molecular signatures across multiple cancers also offers new prospects to move beyond the "One Drug, One Disease" paradigm of pharmaceutical innovation.

Multiple sclerosis (MS) poses a significant challenge in global health, with increasing incidence rates and profound implications that transcend the geographical boundaries. Recent literature has explored the relationship between MS and serum uric acid (SUA) levels, yielding inconclusive findings. A high SUA level is associated with several chronic disorders and has planetary health significance. Explaining person-to-person variations in SUA is therefore important. In this overarching context, despite a multitude of studies on the putative MS and SUA relationship, limitations such as small sample sizes and inconsistent outcomes persist, highlighting the current gaps in understanding this complex relationship. Here, we report a two-sample Mendelian randomization (MR) study that was conducted to estimate causal effects between MS as the exposure and SUA as the outcome. Our analysis leveraged extensive cohort datasets from publicly accessible genome-wide association studies. The inverse variance weighted method in MR indicated that the odds ratios (ORs) of SUA level per unit increase for MS were 1.649 (95% confidence interval [CI] of OR: 1.09-2.488; p = 0.017) and 23.11 (95% CI of OR: 7.04-75.84; p = 2.23 × 10^-7). Leave-one-out sensitivity analyses, horizontal pleiotropy, and Cochran's Q tests showed robustness of results. This study offers support for a causal association between MS incidence and elevated SUA levels. Pleiotropic tests and sensitivity analyses confirmed minimal horizontal pleiotropy effects and the robustness of the causal association. This MR study provides a causal effect between the incidence of MS and SUA level increase.

Melanin is a complex biopolymer with antioxidative, UV-protective, and antimicrobial properties. Melanin is also of interest for bioengineering applications in healthcare. Its production has been frequently observed in several bacteria and higher organisms under specific culture conditions through genetic engineering and chemical mutagenesis. Interestingly, l-DOPA, a precursor to the neurotransmitter dopamine and an effective anti-Parkinsonian drug, has also been frequently observed, at lower levels, along with melanin in the culture of Bacillus thuringiensis, despite the bacterium lacking l-DOPA-producing tyrosinase sequences in the genome. The present study aims to predict the possible l-DOPA-producing enzyme and characterize the melanin biosynthesis pathway in B. thuringiensis var. israelensis MB-24, a strain derived by NTG mutagenesis of entomopathogenic B. thuringiensis var. israelensis B-17. Using metabolomics, we identified the key metabolites involved in melanin production. We also predicted the probable enzyme involved in l-DOPA production through conserved domain search. Sequencing the homogentisate 1,2-dioxygenase (hmgA) gene of MB-24 showed large deletions, suggesting that melanin synthesis may result from accumulated homogentisate in the HGA (Homogentisic acid) pathway. We expressed 4-hydroxyphenyl pyruvate dioxygenase from B. thuringiensis var. israelensis B-17 and characterized the melanin produced by this enzyme through FT-IR (Fourier-Transform Infrared Spectroscopy). The FT-IR analysis further verified that B. thuringiensis var. israelensis MB24 mostly produced pyomelanin. In conclusion, pyomelanin production in B. thuringiensis var. israelensis MB-24 is driven by the homogentisate pathway due to the inability of the mutant bacterium MB-24 to express functional homogentisate 1,2 dioxygenase. These findings inform future industrial and pharmaceutical applications of melanin biosynthesis.