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1. X-intNMF: a cross- and intra-omics regularized NMF framework for multi-omics integration

   https://doi.org/10.1093/bioinformatics/btag046  

   Bui, Tien-Thanh; Xie, Rui; Zhang, Wei (February 2026, Bioinformatics)

   Mathelier, Anthony (Ed.)

   Abstract MotivationThe rapid accumulation of multi-omics data presents a valuable opportunity to advance our understanding of complex diseases and biological systems, driving the development of integrative computational methods. However, the complexity of biological processes, spanning multiple molecular layers and involving intricate regulatory interactions, requires models that can capture both intra- and cross-omics relationships. Most existing integration methods primarily focus on sample-level similarities or intra-omics feature interactions, often neglecting the interactions across different omics layers. This limitation can result in the loss of critical biological information and suboptimal performance. To address this gap, we propose X-intNMF, a network-regularized non-negative matrix factorization (NMF) framework that simultaneously integrates intra- and cross-omics feature interactions into a shared low-dimensional representation (see Fig. 1). By modeling these multi-layered relationships, X-intNMF enhances the representation of biological interactions and improves integration quality and prediction accuracy. ResultsFor evaluation, we applied X-intNMF to predict breast cancer phenotypes and classify clinical outcomes in lung and ovarian cancers using mRNA expression, microRNA expression, and DNA methylation data from TCGA. The results show that X-intNMF consistently outperforms state-of-the-art methods. Ablation studies confirm that incorporating both cross-omics and intra-omics interactions contributes significantly to the model’s improved performance. Additionally, survival analysis on 25 TCGA cancer datasets demonstrates that the integrated multi-omics representation offers strong prognostic value for both overall survival and disease-free status. These findings highlight X-intNMF’s ability to effectively model multi-layered molecular interactions while maintaining interpretability, robustness, and scalability within the NMF framework. Availability and implementationThe source code and datasets supporting this study are publicly available at GitHub (https://github.com/compbiolabucf/X-intNMF) and archived on Zenodo (https://doi.org/10.5281/zenodo.18238385). 

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2. A supervised Bayesian factor model for the identification of multi-omics signatures

   https://doi.org/10.1093/bioinformatics/btae202  

   Gygi, Jeremy P; Konstorum, Anna; Pawar, Shrikant; Aron, Edel; Kleinstein, Steven H; Guan, Leying (May 2024, Bioinformatics)

   Kendziorski, Christina (Ed.)

   Abstract MotivationPredictive biological signatures provide utility as biomarkers for disease diagnosis and prognosis, as well as prediction of responses to vaccination or therapy. These signatures are identified from high-throughput profiling assays through a combination of dimensionality reduction and machine learning techniques. The genes, proteins, metabolites, and other biological analytes that compose signatures also generate hypotheses on the underlying mechanisms driving biological responses, thus improving biological understanding. Dimensionality reduction is a critical step in signature discovery to address the large number of analytes in omics datasets, especially for multi-omics profiling studies with tens of thousands of measurements. Latent factor models, which can account for the structural heterogeneity across diverse assays, effectively integrate multi-omics data and reduce dimensionality to a small number of factors that capture correlations and associations among measurements. These factors provide biologically interpretable features for predictive modeling. However, multi-omics integration and predictive modeling are generally performed independently in sequential steps, leading to suboptimal factor construction. Combining these steps can yield better multi-omics signatures that are more predictive while still being biologically meaningful. ResultsWe developed a supervised variational Bayesian factor model that extracts multi-omics signatures from high-throughput profiling datasets that can span multiple data types. Signature-based multiPle-omics intEgration via lAtent factoRs (SPEAR) adaptively determines factor rank, emphasis on factor structure, data relevance and feature sparsity. The method improves the reconstruction of underlying factors in synthetic examples and prediction accuracy of coronavirus disease 2019 severity and breast cancer tumor subtypes. Availability and implementationSPEAR is a publicly available R-package hosted at https://bitbucket.org/kleinstein/SPEAR. 

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3. VIGAN: Missing view imputation with generative adversarial networks

   https://doi.org/10.1109/BigData.2017.8257992  

   Shang, Chao; Palmer, Aaron; Sun, Jiangwen; Chen, Ko-Shin; Lu, Jin; Bi, Jinbo (December 2017, 2017 IEEE International Conference on Big Data (Big Data))

   In an era when big data are becoming the norm, there is less concern with the quantity but more with the quality and completeness of the data. In many disciplines, data are collected from heterogeneous sources, resulting in multi-view or multi-modal datasets. The missing data problem has been challenging to address in multi-view data analysis. Especially, when certain samples miss an entire view of data, it creates the missing view problem. Classic multiple imputations or matrix completion methods are hardly effective here when no information can be based on in the specific view to impute data for such samples. The commonly-used simple method of removing samples with a missing view can dramatically reduce sample size, thus diminishing the statistical power of a subsequent analysis. In this paper, we propose a novel approach for view imputation via generative adversarial networks (GANs), which we name by VIGAN. This approach first treats each view as a separate domain and identifies domain-to-domain mappings via a GAN using randomly-sampled data from each view, and then employs a multi-modal denoising autoencoder (DAE) to reconstruct the missing view from the GAN outputs based on paired data across the views. Then, by optimizing the GAN and DAE jointly, our model enables the knowledge integration for domain mappings and view correspondences to effectively recover the missing view. Empirical results on benchmark datasets validate the VIGAN approach by comparing against the state of the art. The evaluation of VIGAN in a genetic study of substance use disorders further proves the effectiveness and usability of this approach in life science. 

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4. Deep learning-based phenotype imputation on population-scale biobank data increases genetic discoveries

   https://doi.org/10.1038/s41588-023-01558-w  

   An, Ulzee; Pazokitoroudi, Ali; Alvarez, Marcus; Huang, Lianyun; Bacanu, Silviu; Schork, Andrew J; Kendler, Kenneth; Pajukanta, Päivi; Flint, Jonathan; Zaitlen, Noah; et al (December 2023, Nature Genetics)

   Abstract Biobanks that collect deep phenotypic and genomic data across many individuals have emerged as a key resource in human genetics. However, phenotypes in biobanks are often missing across many individuals, limiting their utility. We propose AutoComplete, a deep learning-based imputation method to impute or ‘fill-in’ missing phenotypes in population-scale biobank datasets. When applied to collections of phenotypes measured across ~300,000 individuals from the UK Biobank, AutoComplete substantially improved imputation accuracy over existing methods. On three traits with notable amounts of missingness, we show that AutoComplete yields imputed phenotypes that are genetically similar to the originally observed phenotypes while increasing the effective sample size by about twofold on average. Further, genome-wide association analyses on the resulting imputed phenotypes led to a substantial increase in the number of associated loci. Our results demonstrate the utility of deep learning-based phenotype imputation to increase power for genetic discoveries in existing biobank datasets. 

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5. Predicting implementation of response to intervention in math using elastic net logistic regression

   https://doi.org/10.3389/fpsyg.2024.1410396  

   Wang, Qi; Hall, Garret J; Zhang, Qian; Comella, Sara (October 2024, Frontiers in Psychology)

   IntroductionThe primary objective of this study was to identify variables that significantly influence the implementation of math Response to Intervention (RTI) at the school level, utilizing the ECLS-K: 2011 dataset. MethodsDue to missing values in the original dataset, a Random Forest algorithm was employed for data imputation, generating a total of 10 imputed datasets. Elastic net logistic regression, combined with nested cross-validation, was applied to each imputed dataset, potentially resulting in 10 models with different variables. Variables for the models derived from the imputed datasets were selected using four methods, leading to four candidate models for final selection. These models were assessed based on their performance of prediction accuracy, culminating in the selection of the final model that outperformed the others. Results and discussionMethod₅₀and Method_coefemerged as the most effective, achieving a balanced accuracy of 0.852. The ultimate model selected relevant variables that effectively predicted RTI. The predictive accuracy of the final model was also demonstrated by the receiver operating characteristic (ROC) plot and the corresponding area under the curve (AUC) value, indicating its ability to accurately forecast math RTI implementation in schools for the following year. 

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