Metabolomics and proteomics generate large, complex datasets that reflect the state of a biological system. Multi-omics is the integration of these disparate methods and data to gain a clearer picture of the biological state. Multi-omic studies of the proteome and metabolome are becoming more common as mass spectrometry technology continues to be democratized. However, knowledge extraction through integration of these data remains challenging. Here we show that connections between these omic layers can be discovered through a combination of machine learning and model interpretation. We find that SHAP values connecting proteins to metabolites are valid experimentally, and reveal also largely new connections. Further, clustering the magnitudes of protein control over all metabolites enabled prediction of gene five gene functions, each of which was validated experimentally. We accurately predicted that two uncharacterized genes in yeast modulate mitochondrial translation, YJR120W and YLD157C.We also predict and validate functions for several incompletely characterized genes, including SDH9, ISC1, and FMP52. Our work demonstrates that multi-omic analysis with machine learning (MIMaL) is a new lens that reveals new insight from multi-omic data that would not be possible using any omic layer alone.

Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decision over which tools to use and how to combine them. Therefore, it is an unmet need to conceptualize how to integrate such data and implement and validate pipelines in different cases. We have designed a conceptual framework (STATegra), aiming it to be as generic as possible for multi-omics analysis, combining available multi-omic anlaysis tools (machine learning component analysis, non-parametric data combination, and a multi-omics exploratory analysis) in a step-wise manner. While in several studies, we have previously combined those integrative tools, here, we provide a systematic description of the STATegra framework and its validation using two The Cancer Genome Atlas (TCGA) case studies. For both, the Glioblastoma and the Skin Cutaneous Melanoma (SKCM) cases, we demonstrate an enhanced capacity of the framework (and beyond the individual tools) to identify features and pathways compared to single-omics analysis. Such an integrative multi-omics analysis framework for identifying features and components facilitates the discovery of new biology. Finally, we provide several options for applying the STATegra framework when parametric assumptions are fulfilled and for the case when not all the samples are profiled for all omics. The STATegra framework is built using several tools, which are being integrated step-by-step as OpenSource in the STATegRa Bioconductor package.1

The global multiomics market, valued at $3.11 billion in 2025, is projected to experience robust growth, exhibiting a compound annual growth rate (CAGR) of 15.26% from 2025 to 2033. This expansion is driven by several key factors. Advancements in sequencing technologies, particularly next-generation sequencing (NGS), are enabling researchers to analyze multiple omics datasets simultaneously, providing a more comprehensive understanding of complex biological systems. This holistic approach is proving invaluable in drug discovery and development, accelerating the identification of novel therapeutic targets and biomarkers. Furthermore, the increasing prevalence of chronic diseases, such as cancer and neurodegenerative disorders, is fueling demand for more precise diagnostic and therapeutic tools, bolstering the multiomics market. Growing investments in research and development across both academia and the pharmaceutical and biotechnology sectors further contribute to this market's rapid growth. The integration of artificial intelligence (AI) and machine learning (ML) in multiomics data analysis is also significantly impacting the field, enabling faster and more accurate interpretations of complex datasets. The market segmentation reveals significant opportunities across various product types, platforms, and applications. While instruments and reagents constitute major segments, the 'Other Products' category, encompassing software and data analysis tools, is experiencing rapid growth due to the increasing complexity of multiomics data. Single-cell multiomics, offering higher resolution and insights into cellular heterogeneity, is gaining traction over bulk multiomics. Within platforms, genomics maintains a dominant position, followed by transcriptomics and proteomics. However, integrated omics platforms, offering a more comprehensive analysis of multiple datasets simultaneously, are showing significant potential for future growth. Oncology and neurology are leading application areas, with substantial research focused on developing personalized medicine approaches leveraging multiomics data. The academic and research institutes segment remains a key end-user, while pharmaceutical and biotechnology companies are increasingly adopting multiomics for drug discovery and development, promising sustained long-term market growth. Competition among established players like Illumina, Thermo Fisher Scientific, and Agilent Technologies, alongside emerging innovative companies, drives further market dynamism and technological advancement. Recent developments include: February 2024: Vizzhy Inc. launched the world's inaugural Multiomics Lab in Bengaluru, India, heralding a major advancement in healthcare innovation. Equipped with cutting-edge tools and health AI technology, the lab enables physicians to pinpoint root causes and offer personalized recommendations for their patients.September 2023: MGI, a provider of technology and tools for life science, introduced the DCS Lab Initiative to stimulate crucial scientific research. This initiative encourages large-scale multiomics laboratories. Under the initiative, the organization offers products for numerous applications, including cell omics, DNA sequencing, and spatial omics based on DNBSEQ technologies, to specified research institutions globally.April 2023: Biomodal, formerly Cambridge Epigenetix, introduced a new duet multiomics solution that can enable simultaneous phased reading of epigenetic and genetic information in a single, low-volume sample.. Key drivers for this market are: Rising Demand for Single-cell Multiomics and Advancements in Omics Technologies, Increasing Investment in Genomics R&D; Growing Demand for Personalized Medicine. Potential restraints include: Rising Demand for Single-cell Multiomics and Advancements in Omics Technologies, Increasing Investment in Genomics R&D; Growing Demand for Personalized Medicine. Notable trends are: The Bulk Multiomics Segment is Expected to Hold the Largest Share of the Market.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies predominantly to nuclear material. Many aspects of disease pathology are mediated by the deposition of nucleic acid containing immune complexes, which also induce the type 1interferon response, a characteristic feature of SLE. Notably, SLE is remarkably heterogeneous, with a variety of organs involved in different individuals, who also show variation in disease severity related to their ancestries. Here, we probed one potential contribution to disease heterogeneity as well as a possible source of immunoreactive nucleic acids by exploring the expression of human endogenous retroviruses (HERVs). We investigated the expression of HERVs in SLE and their potential relationship to SLE features and the expression of biochemical pathways, including the interferon gene signature (IGS). Towards this goal, we analyzed available and new RNA-Seq data from two independent whole blood studies using Telescope. We identified 481 locus specific HERV encoding regions that are differentially expressed between case and control individuals with only 14% overlap of differentially expressed HERVs between these two datasets. We identified significant differences between differentially expressed HERVs and non-differentially expressed HERVs between the two datasets. We also characterized the host differentially expressed genes and tested their association with the differentially expressed HERVs. We found that differentially expressed HERVs were significantly more physically proximal to host differentially expressed genes than non-differentially expressed HERVs. Finally, we capitalized on locus specific resolution of HERV mapping to identify key molecular pathways impacted by differential HERV expression in people with SLE.

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The integration of multi-omic data sets can provide unique information about molecular processes in a cell. Despite the development of many tools to extract information from such data sets, there are limited strategies to systematically extract mechanistic hypotheses from them. We here present COSMOS (Causal Oriented Search of Multi-Omic Space), a method that integrates cell signaling pathways, transcriptional, and metabolics data sets. COSMOS leverages extensive prior knowledge of interactions between biomolecules with computational methods to estimate activities of transcription factors and kinases as well as network-level causal reasoning. COSMOS can provide mechanistic explanations for experimental observations across multiple omic data sets. We applied COSMOS to a dataset comprising transcriptomic, phosphoproteomic, and metabolomic data from nine renal cell carcinoma patients comparing healthy non affected kidney tissue and kidney cancer. We used COSMOS to generate novel hypotheses such as the impact of CDK7 on nucleoside metabolism and its influence on citrulline production, that we validated experimentally. We expect that our freely available method will be broadly useful to extract mechanistic insights from multi-omic studies.

Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels. In examining 3,080 tumor samples from 8 cancer types in The Cancer Genome Atlas, rDriver predicted 1,389 driver mutations. Compared with existing tools, rDriver identified more low frequency mutations associated with lineage specific functional properties, timing of occurrence and patient survival. Evaluation of rDriver predictions using engineered cell-line models resulted in a positive predictive value of 0.94 in PIK3CA genes. Our study highlights the importance of integrating multi-omic data in predicting cancer driver mutations and provides a statistically rigorous solution for cancer target discovery and development.

Glioblastoma multiforme (GBM) is one of the most aggressive types of cancer and exhibits profound genetic and epigenetic heterogeneity, making the development of an effective treatment a major challenge. The recent incorporation of molecular features into the diagnosis of GBM patients has led to an improved categorisation into various tumour subtypes with different prognoses and disease management. In this work, we have exploited the benefits of genome-wide multi-omic approaches to identify potential molecular vulnerabilities existing in GBM patients. Integration of gene expression and DNA methylation data from both bulk GBM and patient-derived GBM stem cell lines has revealed the presence of major sources of GBM variability, pinpointing subtype-specific tumour vulnerabilities amenable to pharmacological interventions. In this sense, inhibition of the AP1, SMAD3 and RUNX1 / RUNX2 pathways, in combination or not with the chemotherapeutic agent temozolomide, led to the subtype-specific impairment of tumour growth, particularly in the context of the aggressive, mesenchymal-like subtype. These results emphasize the involvement of these molecular pathways in the development of GBM and have potential implications for the development of personalized therapeutic approaches.

BACKGROUND: Genomic prediction (GP) based on single nucleotide polymorphisms (SNP) has become a broadly used tool to increase the gain of selection in plant breeding. However, using predictors that are biologically closer to the phenotypes such as transcriptome and metabolome may increase the prediction ability in GP. The objectives of this study were to (i) assess the prediction ability for three phenotypic traits using different omic datasets including sequence variants (SV), deleterious SV (dSV), tolerant SV (tSV), expression presence/absence variation (ePAV), gene expression (GE), transcript expression (TE), and metabolites (M) as single predictors in comparison to those using a SNP array; (ii) investigate the improvement in prediction ability when combining multiple omic datasets information to predict phenotypic variation in barley breeding programs; (iii) explore the relationship between genes and metabolites to unravel the metabolic pathway of the three above mentioned phenotypic traits. RESULTS: The prediction ability from genomic best linear unbiased prediction (GBLUP) for the three traits using dSV information was higher than when using tSV, all SV information, or the SNP array. Any predictors from the transcriptome (GE, TE, as well as ePAV) and metabolome provided higher prediction abilities compared to the SNP array and SV on average across the three traits. In addition, some (di)-similarity existed between different omic datasets, and therefore provided complementary biological perspectives to phenotypic variation. Optimal combining the information of dSV, TE, ePAV, as well as metabolites into GP models could improve the prediction ability over that of the single predictors alone. CONCLUSIONS: The use of integrated omic datasets in GP model is highly recommended. Furthermore, we evaluated a cost-effective approach generating 3’end mRNA sequencing with transcriptome data extracted from seedling without losing prediction ability in comparison to the full-length mRNA sequencing, paving the path for the use of such prediction methods in commercial breeding programs.

Multiomics profiling provides a holistic picture of a condition being examined and captures the complexity of signaling events, beginning from the original cause (environmental or genetic), to downstream functional changes at multiple molecular layers. Pathway enrichment analysis has been used with multiomics data sets to characterize signaling mechanisms. However, technical and biological variability between these layered data limit an integrative computational analyses. We present a Boolean network-based method, multiomics Boolean Omics Network Invariant-Time Analysis (mBONITA), to integrate omics data sets that quantify multiple molecular layers. mBONITA utilizes prior knowledge networks to perform topology-based pathway analysis. In addition, mBONITA identifies genes that are consistently modulated across molecular measurements by combining observed fold-changes and variance, with a measure of node (i.e., gene or protein) influence over signaling, and a measure of the strength of evidence for that gene across data sets. We used mBONITA to integrate multiomics data sets from RAMOS B cells treated with the immunosuppressant drug cyclosporine A under varying O2 tensions to identify pathways involved in hypoxia-mediated chemotaxis. We compare mBONITA’s performance with 6 other pathway analysis methods designed for multiomics data and show that mBONITA identifies a set of pathways with evidence of modulation across all omics layers. mBONITA is freely available at https://github.com/Thakar-Lab/mBONITA.

We provide a single-nuclei RNA-sequencing (snRNA-seq) dataset derived from four COVID-19 patients, generated using the 10x Chromium Next GEM Single Cell v3.1 kit. For our study, these were integrated with snRNA-seq data with 12 publicly available sc/snRNA-seq datasets, comprising organ donor lung samples (n=89) and COVID-19 lung tissue samples (n=51). Additionally, we provide a spatial transcriptomic dataset characterizing different histopathological stages of diffuse alveolar damage, across a cohort of 33 COVID-19 patients. This was generated using the Nanostring Whole Transcriptome Assay (WTA) with regions of interest (ROIs) sized 400 µm² each. This integrated multi-omics analysis of snRNA-seq, histology, and spatial transcriptomics data, is available for exploration and download via our web portal: https://covid19-multiomicatlas.cellgeni.sanger.ac.uk/.

The Multiomics Market offers a range of products, including instruments, consumables, software, and services. Instruments include sequencing systems, mass spectrometers, and flow cytometers. Consumables encompass reagents, kits, and microarrays. Software solutions provide data analysis and visualization capabilities. Services include sample preparation, data analysis, and interpretation. Recent developments include: September 2023: The chromium single-cell gene expression flex assay manufactured by 10x Genomics Inc. now offers high throughput multi-omic cellular profiling as a commercially available capability thanks to the introduction of a new kit. Researchers and their options may detect simultaneous gene and protein expression, which can be expanded at a greater scale thanks to the new kit, which makes the multi-omic characterization of cell populations simple and efficient. The company's product portfolio was able to grow due to this technique., February 2023: Becton, Dickinson, and Company introduced the Rhapsody HT Xpress System, a high-throughput single-cell multiomics platform, to broaden the field of scientific research. With up to eight times more cells per sample than previous BD single-cell analyzers, this innovative technology allows scientists to extract, label, and analyze individual cells at a high sample throughput. This plan should assist the business in expanding its product's uses and serving more clients.. Notable trends are: Rising integration of multi-omics data is driving the market growth.

Data and intermediate structures for "Elucidating Human Milk Oligosaccharide biosynthetic genes through network-based multiomics integration"

The project involves the comparison of gene expression data and estimated flux across over 44 million models of HMO biosynthesis. Here we provide intermediate objects to simplify the task of reproducing our calculations.

Raw/Input data (raw.zip); data_HMO.xlsx is the central dataset including HMO concentrations and gene expression data. Other files are .csv exports from data_HMO.xlsx to circumvent a temporary bug in the xlsx reading package. They should not differ from the original file and are provided to facilitate code readability.

(models_split.zip) HMO biosynthesis models generated through network generation ( /code/1.flux/A) and enumeration (/code/1.flux/B)

(scores_spllit.zip) Correlation (R) and correlation p-values (P) between estimated flux and observed gene expression for corresponding genes (/code/1.flux/C)

(big_mat..zip) Intermediate matrixes containing gene-linkage scores, models score, model classifications and other information generated/used by the Flux-Expression Comparision code (/code/3.flux_expression)

We have developed a web-based platform for HTT PPI visualization, exploration, and multi-omic integration called HTT-OMNI. We demonstrate the utility of this platform not only for exploring and filtering existing huntingtin (HTT) PPIs, but also for investigating user-generated omics datasets. For example, we demonstrate the comparison of a published HTT IP-MS experiment, performed in the striatum brain region of a mouse HD model, to unpublished HTT IP-MS experiments in the cortex brain region. Overall, HTT-OMNI summarizes and integrates known HTT PPIs with polyQ-dependent transcriptome and proteome measurements, providing an all-in-one exploratory platform that facilitates the prioritization of target genes that may contribute to HD pathogenesis.

Populus trichocarpa is an important biofuel feedstock that has been the target of extensive research and is emerging as a model organism for plants, especially woody perennials. This research has generated several large ‘omics datasets. However, only few studies in Populus have attempted to integrate various data types. This review will summarize various ‘omics data layers, focusing on their application in Populus species. Subsequently, network and signal processing techniques for the integration and analysis of these data types will be discussed, with particular reference to examples in Populus.

Additional file 2. Supplementary Tables.

Supplementary Material 2.

Two public validation cohorts were utilized in the MT-Pilot study, the Cancer Genome Atlas (TCGA) and cohort-1 Johns Hopkins University (JHU). These datasets included DNA, RNA, clinical data, and tissue protein analytes analyzed for survival outcome prediction using AI/Machine Learning modeling.

This project contains raw data, intermediate files and results is a re-analysis of the publicly available dataset from the PRIDE dataset PXD003791. The RAW files were processed using ThermoRawFileParser, SearchGUI and PeptideShaker through standard settings (see ‘Data Processing Protocol’). This reanalysis work is part of the MetaPUF (MetaProteomics with Unknown Function) project, which is a collaboration between EMBL-EBI and the University of Luxembourg. The dataset was selected with the following conditions: 1. It has been made publicly available in PRIDE and focuses on metaproteomics of the human gut; 2. The corresponding metagenomics assemblies were also available from ENA (European Nucleotide Archive) or MGnify. The processed peptide reports for each sample are available to view at the contig level on the MGnify website. In total, the reanalysis identified 59,613 unique proteins from 36 samples.

Additional file 5: Table S1: MSEA top pathways. Table S2: Scores of pathways after applying 12 topological algorithms. Table S3: Detailed information of key drivers in wKDA network. Table S4: The details of hub genes. Table S5: The details of TFs. Table S6: Detailed results of drug repositioning results.