Structure-revealing data fusion

BACKGROUND: Analysis of data from multiple sources has the potential to enhance knowledge discovery by capturing underlying structures, which are, otherwise, difficult to extract. Fusing data from multiple sources has already proved useful in many applications in social network analysis, signal processing and bioinformatics. However, data fusion is challenging since data from multiple sources are often (i) heterogeneous (i.e., in the form of higher-order tensors and matrices), (ii) incomplete, and (iii) have both shared and unshared components. In order to address these challenges, in this paper, we introduce a novel unsupervised data fusion model based on joint factorization of matrices and higher-order tensors. RESULTS: While the traditional formulation of coupled matrix and tensor factorizations modeling only shared factors fails to capture the underlying structures in the presence of both shared and unshared factors, the proposed data fusion model has the potential to automatically reveal shared and unshared components through modeling constraints. Using numerical experiments, we demonstrate the effectiveness of the proposed approach in terms of identifying shared and unshared components. Furthermore, we measure a set of mixtures with known chemical composition using both LC-MS (Liquid Chromatography - Mass Spectrometry) and NMR (Nuclear Magnetic Resonance) and demonstrate that the structure-revealing data fusion model can (i) successfully capture the chemicals in the mixtures and extract the relative concentrations of the chemicals accurately, (ii) provide promising results in terms of identifying shared and unshared chemicals, and (iii) reveal the relevant patterns in LC-MS by coupling with the diffusion NMR data. CONCLUSIONS: We have proposed a structure-revealing data fusion model that can jointly analyze heterogeneous, incomplete data sets with shared and unshared components and demonstrated its promising performance as well as potential limitations on both simulated and real data. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-239) contains supplementary material, which is available to authorized users

Pathway-Based Multi-Omics Data Integration for Breast Cancer Diagnosis and Prognosis.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017

Cancer Subtyping Detection using Biomarker Discovery in Multi-Omics Tensor Datasets

This thesis begins with a thorough review of research trends from 2015 to 2022, examining the challenges and issues related to biomarker discovery in multi-omics datasets. The review covers areas of application, proposed methodologies, evaluation criteria used to assess performance, as well as limitations and drawbacks that require further investigation and improvement. This comprehensive overview serves to provide a deeper understanding of the current state of research in this field and the opportunities for future research. It will be particularly useful for those who are interested in this area of study and seeking to expand their knowledge. In the second part of this thesis, a novel methodology is proposed for the identification of significant biomarkers in a multi-omics colon cancer dataset. The integration of clinical features with biomarker discovery has the potential to facilitate the early identification of mortality risk and the development of personalized therapies for a range of diseases, including cancer and stroke. Recent advancements in “omics� technologies have opened up new avenues for researchers to identify disease biomarkers through system-level analysis. Machine learning methods, particularly those based on tensor decomposition techniques, have gained popularity due to the challenges associated with integrative analysis of multi-omics data owing to the complexity of biological systems. Despite extensive efforts towards discovering disease-associated biomolecules by analyzing data from various “omics� experiments, such as genomics, transcriptomics, and metabolomics, the poor integration of diverse forms of 'omics' data has made the integrative analysis of multi-omics data a daunting task. Our research includes ANOVA simultaneous component analysis (ASCA) and Tucker3 modeling to analyze a multivariate dataset with an underlying experimental design. By comparing the spaces spanned by different model components we showed how the two methods can be used for confirmatory analysis and provide complementary information. we demonstrated the novel use of ASCA to analyze the residuals of Tucker3 models to find the optimum one. Increasing the model complexity to more factors removed the last remaining ASCA detectable structure in the residuals. Bootstrap analysis of the core matrix values of the Tucker3 models used to check that additional triads of eigenvectors were needed to describe the remaining structure in the residuals. Also, we developed a new simple, novel strategy for aligning Tucker3 bootstrap models with the Tucker3 model of the original data so that eigenvectors of the three modes, the order of the values in the core matrix, and their algebraic signs match the original Tucker3 model without the need for complicated bookkeeping strategies or performing rotational transformations. Additionally, to avoid getting an overparameterized Tucker3 model, we used the bootstrap method to determine 95% confidence intervals of the loadings and core values. Also, important variables for classification were identified by inspection of loading confidence intervals. The experimental results obtained using the colon cancer dataset demonstrate that our proposed methodology is effective in improving the performance of biomarker discovery in a multi-omics cancer dataset. Overall, our study highlights the potential of integrating multi-omics data with machine learning methods to gain deeper insights into the complex biological mechanisms underlying cancer and other diseases. The experimental results using NIH colon cancer dataset demonstrate that the successful application of our proposed methodology in cancer subtype classification provides a foundation for further investigation into its utility in other disease areas

A Review on Data Fusion of Multidimensional Medical and Biomedical Data

Data fusion aims to provide a more accurate description of a sample than any one source of data alone. At the same time, data fusion minimizes the uncertainty of the results by combining data from multiple sources. Both aim to improve the characterization of samples and might improve clinical diagnosis and prognosis. In this paper, we present an overview of the advances achieved over the last decades in data fusion approaches in the context of the medical and biomedical fields. We collected approaches for interpreting multiple sources of data in different combinations: image to image, image to biomarker, spectra to image, spectra to spectra, spectra to biomarker, and others. We found that the most prevalent combination is the image-to-image fusion and that most data fusion approaches were applied together with deep learning or machine learning methods

Machine and deep learning meet genome-scale metabolic modeling

Omic data analysis is steadily growing as a driver of basic and applied molecular biology research. Core to the interpretation of complex and heterogeneous biological phenotypes are computational approaches in the fields of statistics and machine learning. In parallel, constraint-based metabolic modeling has established itself as the main tool to investigate large-scale relationships between genotype, phenotype, and environment. The development and application of these methodological frameworks have occurred independently for the most part, whereas the potential of their integration for biological, biomedical, and biotechnological research is less known. Here, we describe how machine learning and constraint-based modeling can be combined, reviewing recent works at the intersection of both domains and discussing the mathematical and practical aspects involved. We overlap systematic classifications from both frameworks, making them accessible to nonexperts. Finally, we delineate potential future scenarios, propose new joint theoretical frameworks, and suggest concrete points of investigation for this joint subfield. A multiview approach merging experimental and knowledge-driven omic data through machine learning methods can incorporate key mechanistic information in an otherwise biologically-agnostic learning process

Integrative methods for analyzing big data in precision medicine

We provide an overview of recent developments in big data analyses in the context of precision medicine and health informatics. With the advance in technologies capturing molecular and medical data, we entered the area of “Big Data” in biology and medicine. These data offer many opportunities to advance precision medicine. We outline key challenges in precision medicine and present recent advances in data integration-based methods to uncover personalized information from big data produced by various omics studies. We survey recent integrative methods for disease subtyping, biomarkers discovery, and drug repurposing, and list the tools that are available to domain scientists. Given the ever-growing nature of these big data, we highlight key issues that big data integration methods will face

Machine learning methods for omics data integration

High-throughput technologies produce genome-scale transcriptomic and metabolomic (omics) datasets that allow for the system-level studies of complex biological processes. The limitation lies in the small number of samples versus the larger number of features represented in these datasets. Machine learning methods can help integrate these large-scale omics datasets and identify key features from each dataset. A novel class dependent feature selection method integrates the F statistic, maximum relevance binary particle swarm optimization (MRBPSO), and class dependent multi-category classification (CDMC) system. A set of highly differentially expressed genes are pre-selected using the F statistic as a filter for each dataset. MRBPSO and CDMC function as a wrapper to select desirable feature subsets for each class and classify the samples using those chosen class-dependent feature subsets. The results indicate that the class-dependent approaches can effectively identify unique biomarkers for each cancer type and improve classification accuracy compared to class independent feature selection methods. The integration of transcriptomics and metabolomics data is based on a classification framework. Compared to principal component analysis and non-negative matrix factorization based integration approaches, our proposed method achieves 20-30% higher prediction accuracies on Arabidopsis tissue development data. Metabolite-predictive genes and gene-predictive metabolites are selected from transcriptomic and metabolomic data respectively. The constructed gene-metabolite correlation network can infer the functions of unknown genes and metabolites. Tissue-specific genes and metabolites are identified by the class-dependent feature selection method. Evidence from subcellular locations, gene ontology, and biochemical pathways support the involvement of these entities in different developmental stages and tissues in Arabidopsis

Integrative methods for analysing big data in precision medicine

We provide an overview of recent developments in big data analyses in the context of precision medicine and health informatics. With the advance in technologies capturing molecular and medical data, we entered the area of “Big Data” in biology and medicine. These data offer many opportunities to advance precision medicine. We outline key challenges in precision medicine and present recent advances in data integration-based methods to uncover personalized information from big data produced by various omics studies. We survey recent integrative methods for disease subtyping, biomarkers discovery, and drug repurposing, and list the tools that are available to domain scientists. Given the ever-growing nature of these big data, we highlight key issues that big data integration methods will face

Explicit–implicit mapping approach to nonlinear blind separation of sparse nonnegative dependent sources from a single mixture: pure component extraction from nonlinear mixture mass spectra

The nonlinear, nonnegative single-mixture blind source separation (BSS) problem consists of decomposing observed nonlinearly mixed multicomponent signal into nonnegative dependent component (source) signals. The problem is difficult and is a special case of the underdetermined BSS problem. However, it is practically relevant for the contemporary metabolic profiling of biological samples when only one sample is available for acquiring mass spectra ; afterwards, the pure components are extracted. Herein, we present a method for the blind separation of nonnegative dependent sources from a single, nonlinear mixture. First, an explicit feature map is used to map a single mixture into a pseudo multi-mixture. Second, an empirical kernel map is used for implicit mapping of a pseudo multi-mixture into a high-dimensional reproducible kernel Hilbert space (RKHS). Under sparse probabilistic conditions that were previously imposed on sources, the single-mixture nonlinear problem is converted into an equivalent linear, multiple-mixture problem that consists of the original sources and their higher order monomials. These monomials are suppressed by robust principal component analysis, hard-, soft- and trimmed thresholding. Sparseness constrained nonnegative matrix factorizations in RKHS yield sets of separated components. Afterwards, separated components are annotated with the pure components from the library using the maximal correlation criterion. The proposed method is depicted with a numerical example that is related to the extraction of 8 dependent components from 1 nonlinear mixture. The method is further demonstrated on 3 nonlinear chemical reactions of peptide synthesis in which 25, 19 and 28 dependent analytes are extracted from 1 nonlinear mixture mass spectra. The goal application of the proposed method is, in combination with other separation techniques, mass spectrometry-based non-targeted metabolic profiling, such as biomarker identification studies