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Tissue heterogeneity is a major confounding factor in studying individual populations that cannot be resolved directly by global profiling. Experimental solutions to mitigate tissue heterogeneity are expensive, time consuming, inapplicable to existing data, and may alter the original gene expression patterns. Here we ask whether it is possible to deconvolute two-source mixed expressions (estimating both proportions and cell-specific profiles) from two or more heterogeneous samples without requiring any prior knowledge. Supported by a well-grounded mathematical framework, we argue that both constituent proportions and cell-specific expressions can be estimated in a completely unsupervised mode when cell-specific marker genes exist, which do not have to be known a priori, for each of constituent cell types. We demonstrate the performance of unsupervised deconvolution on both simulation and real gene expression data, together with perspective discussions.
Motivation : Molecular signatures for diagnosis or prognosis estimated from large-scale gene expression data often lack robustness and stability, rendering their biological interpretation challenging. Increasing the signatures interpretability and st
Tiling arrays make possible a large scale exploration of the genome thanks to probes which cover the whole genome with very high density until 2 000 000 probes. Biological questions usually addressed are either the expression difference between two c
Exploring the genetic basis of heritable traits remains one of the central challenges in biomedical research. In simple cases, single polymorphic loci explain a significant fraction of the phenotype variability. However, many traits of interest appea
By combining various cancer cell line (CCL) drug screening panels, the size of the data has grown significantly to begin understanding how advances in deep learning can advance drug response predictions. In this paper we train >35,000 neural network
Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy legislation, meta-analyses are frequentl