Do you want to publish a course? Click here

A feasible roadmap for unsupervised deconvolution of two-source mixed gene expressions

181   0   0.0 ( 0 )
 Added by Yue Wang
 Publication date 2013
and research's language is English




Ask ChatGPT about the research

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.



rate research

Read More

151 - Anne-Claire Haury 2010
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 stability across perturbations of a given dataset and, if possible, across datasets, is urgently needed to ease the discovery of important biological processes and, eventually, new drug targets. Results : We propose a new method to construct signatures with increased stability and easier interpretability. The method uses a gene network as side interpretation and enforces a large connectivity among the genes in the signature, leading to signatures typically made of genes clustered in a few subnetworks. It combines the recently proposed graph Lasso procedure with a stability selection procedure. We evaluate its relevance for the estimation of a prognostic signature in breast cancer, and highlight in particular the increase in interpretability and stability of the signature.
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 conditions or the detection of transcribed regions. In this work we propose to consider simultaneously both questions as an unsupervised classification problem by modeling the joint distribution of the two conditions. In contrast to previous methods, we account for all available information on the probes as well as biological knowledge like annotation and spatial dependence between probes. Since probes are not biologically relevant units we propose a classification rule for non-connected regions covered by several probes. Applications to transcriptomic and ChIP-chip data of Arabidopsis thaliana obtained with a NimbleGen tiling array highlight the importance of a precise modeling and the region classification.
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 appear to be subject to multifactorial control by groups of genetic loci instead. Accurate detection of such multivariate associations is nontrivial and often hindered by limited power. At the same time, confounding influences such as population structure cause spurious association signals that result in false positive findings if they are not accounted for in the model. Here, we propose LMM-Lasso, a mixed model that allows for both, multi-locus mapping and correction for confounding effects. Our approach is simple and free of tuning parameters, effectively controls for population structure and scales to genome-wide datasets. We show practical use in genome-wide association studies and linkage mapping through retrospective analyses. In data from Arabidopsis thaliana and mouse, our method is able to find a genetic cause for significantly greater fractions of phenotype variation in 91% of the phenotypes considered. At the same time, our model dissects this variability into components that result from individual SNP effects and population structure. In addition to this increase of genetic heritability, enrichment of known candidate genes suggests that the associations retrieved by LMM-Lasso are more likely to be genuine.
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 models, sweeping over common featurization techniques. We found the RNA-seq to be highly redundant and informative even with subsets larger than 128 features. We found the inclusion of single nucleotide polymorphisms (SNPs) coded as count matrices improved model performance significantly, and no substantial difference in model performance with respect to molecular featurization between the common open source MOrdred descriptors and Dragon7 descriptors. Alongside this analysis, we outline data integration between CCL screening datasets and present evidence that new metrics and imbalanced data techniques, as well as advances in data standardization, need to be developed.
77 - Olga Zolotareva 2020
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 frequently employed to pool local results. However, if class labels are inhomogeneously distributed between cohorts, their accuracy may drop. Flimma (https://exbio.wzw.tum.de/flimma/) addresses this issue by implementing the state-of-the-art workflow limma voom in a privacy-preserving manner, i.e. patient data never leaves its source site. Flimma results are identical to those generated by limma voom on combined datasets even in imbalanced scenarios where meta-analysis approaches fail.
comments
Fetching comments Fetching comments
Sign in to be able to follow your search criteria
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا