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Bayesian methods for improved analysis of single-cell RNA-seq data

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  • Full or part time
    Prof Rattray
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The BitSeq package provides Bayesian methods for inferring the expression level of mRNA transcripts from the computational analysis of large-scale RNA sequencing (RNA-Seq) data (Glaus et al. 2012). BitSeq was shown to perform well in a recent large-scale benchmark study comparing different methods (SEQC/MAQC-III Consortium 2014) and is under constant development to improve accuracy and computation time (Hensman et al. 2014; Papastamoulis et al. 2014). BitSeq works by deconvolving the signal from large numbers of short RNA sequence reads which are derived from different transcripts that may share a significant proportion of their underlying mRNA sequence, e.g. different isoforms or allelic variants of the same gene. This deconvolution allows the inference of the expression-level of closely related transcripts, providing valuable insights into differences in splicing and allele usage across conditions or treatments.

The widespread adoption of single-cell RNA-Seq protocols now allows for transcriptomic profiling of single cells with the potential to revolutionise our understanding of cellular heterogeneity and to leverage this heterogeneity to infer gene regulatory networks. However, the inference of closely related transcripts from single-cell data is challenging as single-cell RNA-Seq experiments tend to be carried out with lower sequencing depth and the sample preparation is more challenging leading to greater biases in the data produced. Inferring transcription expression levels is therefore particularly challenging from single-cell RNA-Seq data. Downstream processing methods to infer regulatory networks are also of great interest and can benefit from improved low-level data analysis. In this project the student will work on a BitSeq analysis pipeline for single-cell RNA-seq processing. Manchester has recently received a £5m award from the UK’s Medical Research Council to establish a clinical single-cell research centre and the student will work with members of the centre to apply and benchmark new methodology developed in the project on clinical single-cell RNA-Seq datasets.


Funding Notes

This project has a Band 1 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.

References

Glaus, Peter, Antti Honkela, and Magnus Rattray. "Identifying differentially expressed transcripts from RNA-seq data with biological variation." Bioinformatics 28.13 (2012): 1721-1728.

Hensman, James, et al. "Fast and accurate approximate inference of transcript expression from RNA-seq data." arXiv preprint arXiv:1412.5995 (2014).

Papastamoulis, Panagiotis, et al. "Improved variational Bayes inference for transcript expression estimation." Statistical applications in genetics and molecular biology 13.2 (2014): 203-216.

SEQC/MAQC-III Consortium. "A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium." Nature Biotechnology 32.9 (2014): 903-914.



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