Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Artificial Intelligence Predicted Overall Survival and Classified Mature B-Cell Neoplasms Based on Immuno-Oncology and Immune Checkpoint Panels

Artificial intelligence (AI) can identify actionable oncology biomarkers. This research integrates our previous analyses of non-Hodgkin lymphoma. We used gene expression and immunohistochemical data, focusing on the immune checkpoint, and added a new analysis of macrophages, including 3D rendering. The AI comprised machine learning (C5, Bayesian network, C&R, CHAID, discriminant analysis, KNN, logistic regression, LSVM, Quest, random forest, random trees, SVM, tree-AS, and XGBoost linear and tree) and artificial neural networks (multilayer perceptron and radial basis function). The series included chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, Burkitt, diffuse large B-cell lymphoma, marginal zone lymphoma, and multiple myeloma, as well as acute myeloid leukemia and pan-cancer series. AI classified lymphoma subtypes and predicted overall survival accurately. Oncogenes and tumor suppressor genes were highlighted (MYC, BCL2, and TP53), along with immune microenvironment markers of tumor-associated macrophages (M2-like TAMs), T-cells and regulatory T lymphocytes (Tregs) (CD68, CD163, MARCO, CSF1R, CSF1, PD-L1/CD274, SIRPA, CD85A/LILRB3, CD47, IL10, TNFRSF14/HVEM, TNFAIP8, IKAROS, STAT3, NFKB, MAPK, PD-1/PDCD1, BTLA, and FOXP3), apoptosis (BCL2, CASP3, CASP8, PARP, and pathway-related MDM2, E2F1, CDK6, MYB, and LMO2), and metabolism (ENO3, GGA3). In conclusion, AI with immuno-oncology markers is a powerful predictive tool. Additionally, a review of recent literature was made

MACHINE LEARNING AND DEEP LEARNING APPROACHES FOR GENE REGULATORY NETWORK INFERENCE IN PLANT SPECIES

The construction of gene regulatory networks (GRNs) is vital for understanding the regulation of metabolic pathways, biological processes, and complex traits during plant growth and responses to environmental cues and stresses. The increasing availability of public databases has facilitated the development of numerous methods for inferring gene regulatory relationships between transcription factors and their targets. However, there is limited research on supervised learning techniques that utilize available regulatory relationships of plant species in public databases. This study investigates the potential of machine learning (ML), deep learning (DL), and hybrid approaches for constructing GRNs in plant species, specifically Arabidopsis thaliana, poplar, and maize. Challenges arise due to limited training data for gene regulatory pairs, especially in less-studied species such as poplar and maize. Nonetheless, our results demonstrate that hybrid models integrating ML and artificial neural network (ANN) techniques significantly outperformed traditional methods in predicting gene regulatory relationships. The best-performing hybrid models achieved over 95% accuracy on holdout test datasets, surpassing traditional ML and ANN models and also showed good accuracy on lignin biosynthesis pathway analysis. Employing transfer learning techniques, this study has also successfully transferred the known knowledge of gene regulation from one species to another, substantially improving performance and manifesting the viability of cross-species learning using deep learning-based approaches. This study contributes to the methodology for growing body of knowledge in GRN prediction and construction for plant species, highlighting the value of adopting hybrid models and transfer learning techniques. This study and the results will help to pave a way for future research on how to learn from known to unknown and will be conductive to the advance of modern genomics and bioinformatics

Pathway-Based Genomics Prediction using Generalized Elastic Net.

We present a novel regularization scheme called The Generalized Elastic Net (GELnet) that incorporates gene pathway information into feature selection. The proposed formulation is applicable to a wide variety of problems in which the interpretation of predictive features using known molecular interactions is desired. The method naturally steers solutions toward sets of mechanistically interlinked genes. Using experiments on synthetic data, we demonstrate that pathway-guided results maintain, and often improve, the accuracy of predictors even in cases where the full gene network is unknown. We apply the method to predict the drug response of breast cancer cell lines. GELnet is able to reveal genetic determinants of sensitivity and resistance for several compounds. In particular, for an EGFR/HER2 inhibitor, it finds a possible trans-differentiation resistance mechanism missed by the corresponding pathway agnostic approach