Biology subjects

Emma Pierson

Publications and source records attributed to Emma Pierson.

4 recordsLinked to original sources

bioRxiv2016

Visualization and analysis of single-cell RNA-seq data by kernel-based similarity learning

Single-cell RNA-seq technologies enable high throughput gene expression measurement of individual cells, and allow the discovery of heterogeneity within cell populations. Measurement of cell-to-cell gene expression similarity is critical to identification, visualization and analysis of cell populations. However, single-cell data introduce challenges to conventional measures of gene expression similarity because of the high level of noise, outliers and dropouts. Here, we propose a novel similarity-learning framework, SIMLR (single-cell interpretation via multi-kernel learning), which learns an appropriate distance metric from the data for dimension reduction, clustering and visualization applications. Benchmarking against state-of-the-art methods for these applications, we used SIMLR to re-analyse seven representative single-cell data sets, including high-throughput droplet-based data sets with tens of thousands of cells. We show that SIMLR greatly improves clustering sensitivity and accuracy, as well as the visualization and interpretability of the data.

Bioinformatics↗

bioRxiv2016

Denoising genome-wide histone ChIP-seq with convolutional neural networks

MotivationChromatin immunoprecipitation sequencing (ChIP-seq) experiments are commonly used to obtain genome-wide profiles of histone modifications associated with different types of functional genomic elements. However, the quality of histone ChIP-seq data is affected by a myriad of experimental parameters such as the amount of input DNA, antibody specificity, ChIP enrichment, and sequencing depth. Making accurate inferences from chromatin profiling experiments that involve diverse experimental parameters is challenging.\n\nResultsWe introduce a convolutional denoising algorithm, Coda, that uses convolutional neural networks to learn a mapping from suboptimal to high-quality histone ChIP-seq data. This overcomes various sources of noise and variability, substantially enhancing and recovering signal when applied to low-quality chromatin profiling datasets across individuals, cell types, and species. Our method has the potential to improve data quality at reduced costs. More broadly, this approach - using a high-dimensional discriminative model to encode a generative noise process - is generally applicable to other biological domains where it is easy to generate noisy data but difficult to analytically characterize the noise or underlying data distribution.\n\nAvailabilityhttps://github.com/kundajelab/coda\n\nContactakundaje@stanford.edu

Bioinformatics↗

bioRxiv2015

ZIFA: Dimensionality reduction for zero-inflated single cell gene expression analysis

Single cell RNA-seq data allows insight into normal cellular function and diseases including cancer through the molecular characterisation of cellular state at the single-cell level. Dimensionality reduction of such high-dimensional datasets is essential for visualization and analysis, but single-cell RNA-seq data is challenging for classical dimensionality reduction methods because of the prevalence of dropout events leading to zero-inflated data. Here we develop a dimensionality reduction method, (Z)ero (I)nflated (F)actor (A)nalysis (ZIFA), which explicitly models the dropout characteristics, and show that it improves modelling accuracy on simulated and biological datasets.

Bioinformatics↗

bioRxiv2014

Sharing and specificity of co-expression networks across 35 human tissues

To understand the regulation of tissue-specific gene expression, the GTEx Consortium generated RNA-seq expression data for more than thirty distinct human tissues. This data provides an opportunity for deriving shared and tissue-specific gene regulatory networks on the basis of co-expression between genes. However, a small number of samples are available for a majority of the tissues, and therefore statistical inference of networks in this setting is highly underpowered. To address this problem, we infer tissue-specific gene co-expression networks for 35 tissues in the GTEx dataset using a novel algorithm, GNAT, that uses a hierarchy of tissues to share data between related tissues. We show that this transfer learning approach increases the accuracy with which networks are learned. Analysis of these networks reveals that tissue-specific transcription factors are hubs that preferentially connect to genes with tissue-specific functions. Additionally, we observe that genes with tissue-specific functions lie at the peripheries of our networks. We identify numerous modules enriched for Gene Ontology functions, and show that modules conserved across tissues are especially likely to have functions common to all tissues, while modules that are upregulated in a particular tissue are often instrumental to tissue-specific function. Finally, we provide a web tool, available at mostafavilab.stat.ubc.ca/GNAT, which allows exploration of gene function and regulation in a tissue-specific manner.\n\nAuthor SummaryCells in different tissues perform very different functions with the same DNA. This requires tissue-specific gene expression and regulation; understanding this tissue-specificity is often instrumental to understanding complex diseases. Here, we use tissue-specific gene expression data to learn tissue-specific gene regulatory networks for 35 human tissues, where two genes are linked if their expression levels are correlated. Learning such networks accurately is difficult because of the large number of possible links between genes and small number of samples. We propose a novel algorithm that combats this problem by sharing data between similar tissues and show that this increases the accuracy with which networks are learned. We provide a web tool for exploring these networks, enabling users to pose diverse queries in a gene-or tissue-centric manner, and facilitating explorations into gene function and regulation.

Bioinformatics↗