SUBIC: A Supervised Bi-Clustering Approach for Precision Medicine

Traditional medicine typically applies one-size-fits-all treatment for the entire patient population whereas precision medicine develops tailored treatment schemes for different patient subgroups. The fact that some factors may be more significant for a specific patient subgroup motivates clinicians and medical researchers to develop new approaches to subgroup detection and analysis, which is an effective strategy to personalize treatment. In this study, we propose a novel patient subgroup detection method, called Supervised Biclustring (SUBIC) using convex optimization and apply our approach to detect patient subgroups and prioritize risk factors for hypertension (HTN) in a vulnerable demographic subgroup (African-American). Our approach not only finds patient subgroups with guidance of a clinically relevant target variable but also identifies and prioritizes risk factors by pursuing sparsity of the input variables and encouraging similarity among the input variables and between the input and target variable

Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task

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

Binary Particle Swarm Optimization based Biclustering of Web usage Data

Web mining is the nontrivial process to discover valid, novel, potentially useful knowledge from web data using the data mining techniques or methods. It may give information that is useful for improving the services offered by web portals and information access and retrieval tools. With the rapid development of biclustering, more researchers have applied the biclustering technique to different fields in recent years. When biclustering approach is applied to the web usage data it automatically captures the hidden browsing patterns from it in the form of biclusters. In this work, swarm intelligent technique is combined with biclustering approach to propose an algorithm called Binary Particle Swarm Optimization (BPSO) based Biclustering for Web Usage Data. The main objective of this algorithm is to retrieve the global optimal bicluster from the web usage data. These biclusters contain relationships between web users and web pages which are useful for the E-Commerce applications like web advertising and marketing. Experiments are conducted on real dataset to prove the efficiency of the proposed algorithms

A Survey on Soft Subspace Clustering

Subspace clustering (SC) is a promising clustering technology to identify clusters based on their associations with subspaces in high dimensional spaces. SC can be classified into hard subspace clustering (HSC) and soft subspace clustering (SSC). While HSC algorithms have been extensively studied and well accepted by the scientific community, SSC algorithms are relatively new but gaining more attention in recent years due to better adaptability. In the paper, a comprehensive survey on existing SSC algorithms and the recent development are presented. The SSC algorithms are classified systematically into three main categories, namely, conventional SSC (CSSC), independent SSC (ISSC) and extended SSC (XSSC). The characteristics of these algorithms are highlighted and the potential future development of SSC is also discussed.Comment: This paper has been published in Information Sciences Journal in 201

Partial mixture model for tight clustering of gene expression time-course

Background: Tight clustering arose recently from a desire to obtain tighter and potentially more informative clusters in gene expression studies. Scattered genes with relatively loose correlations should be excluded from the clusters. However, in the literature there is little work dedicated to this area of research. On the other hand, there has been extensive use of maximum likelihood techniques for model parameter estimation. By contrast, the minimum distance estimator has been largely ignored. Results: In this paper we show the inherent robustness of the minimum distance estimator that makes it a powerful tool for parameter estimation in model-based time-course clustering. To apply minimum distance estimation, a partial mixture model that can naturally incorporate replicate information and allow scattered genes is formulated. We provide experimental results of simulated data fitting, where the minimum distance estimator demonstrates superior performance to the maximum likelihood estimator. Both biological and statistical validations are conducted on a simulated dataset and two real gene expression datasets. Our proposed partial regression clustering algorithm scores top in Gene Ontology driven evaluation, in comparison with four other popular clustering algorithms. Conclusion: For the first time partial mixture model is successfully extended to time-course data analysis. The robustness of our partial regression clustering algorithm proves the suitability of the ombination of both partial mixture model and minimum distance estimator in this field. We show that tight clustering not only is capable to generate more profound understanding of the dataset under study well in accordance to established biological knowledge, but also presents interesting new hypotheses during interpretation of clustering results. In particular, we provide biological evidences that scattered genes can be relevant and are interesting subjects for study, in contrast to prevailing opinion