Inferring meta-covariates in classification

This paper develops an alternative method for gene selection that combines model based clustering and binary classification. By averaging the covariates within the clusters obtained from model based clustering, we define “meta-covariates” and use them to build a probit regression model, thereby selecting clusters of similarly behaving genes, aiding interpretation. This simultaneous learning task is accomplished by an EM algorithm that optimises a single likelihood function which rewards good performance at both classification and clustering. We explore the performance of our methodology on a well known leukaemia dataset and use the Gene Ontology to interpret our results

Joint Clustering and Registration of Functional Data

Curve registration and clustering are fundamental tools in the analysis of functional data. While several methods have been developed and explored for either task individually, limited work has been done to infer functional clusters and register curves simultaneously. We propose a hierarchical model for joint curve clustering and registration. Our proposal combines a Dirichlet process mixture model for clustering of common shapes, with a reproducing kernel representation of phase variability for registration. We show how inference can be carried out applying standard posterior simulation algorithms and compare our method to several alternatives in both engineered data and a benchmark analysis of the Berkeley growth data. We conclude our investigation with an application to time course gene expression

Deep Divergence-Based Approach to Clustering

A promising direction in deep learning research consists in learning representations and simultaneously discovering cluster structure in unlabeled data by optimizing a discriminative loss function. As opposed to supervised deep learning, this line of research is in its infancy, and how to design and optimize suitable loss functions to train deep neural networks for clustering is still an open question. Our contribution to this emerging field is a new deep clustering network that leverages the discriminative power of information-theoretic divergence measures, which have been shown to be effective in traditional clustering. We propose a novel loss function that incorporates geometric regularization constraints, thus avoiding degenerate structures of the resulting clustering partition. Experiments on synthetic benchmarks and real datasets show that the proposed network achieves competitive performance with respect to other state-of-the-art methods, scales well to large datasets, and does not require pre-training steps

Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics.

BackgroundSingle-cell transcriptomics allows researchers to investigate complex communities of heterogeneous cells. It can be applied to stem cells and their descendants in order to chart the progression from multipotent progenitors to fully differentiated cells. While a variety of statistical and computational methods have been proposed for inferring cell lineages, the problem of accurately characterizing multiple branching lineages remains difficult to solve.ResultsWe introduce Slingshot, a novel method for inferring cell lineages and pseudotimes from single-cell gene expression data. In previously published datasets, Slingshot correctly identifies the biological signal for one to three branching trajectories. Additionally, our simulation study shows that Slingshot infers more accurate pseudotimes than other leading methods.ConclusionsSlingshot is a uniquely robust and flexible tool which combines the highly stable techniques necessary for noisy single-cell data with the ability to identify multiple trajectories. Accurate lineage inference is a critical step in the identification of dynamic temporal gene expression

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