4.6 Article

OscoNet: inferring oscillatory gene networks

Journal

BMC BIOINFORMATICS
Volume 21, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s12859-020-03561-y

Keywords

Single-cell; Network analysis; Non-parametric hypothesis test

Funding

  1. MRC [MR/M008908/1]
  2. H2020-EU EU Marie Curie fellowship CONTESSA [660388]
  3. Wellcome Trust Senior Research Fellowship [106185/Z/14/Z]
  4. Sir Henry Wellcome Fellowship [201380/Z/16/Z]
  5. University of Manchester Wellcome Trust funds
  6. Medical Research Council [MR/M008908/1] Funding Source: researchfish
  7. Marie Curie Actions (MSCA) [660388] Funding Source: Marie Curie Actions (MSCA)
  8. Wellcome Trust [106185/Z/14/Z, 201380/Z/16/Z] Funding Source: Wellcome Trust

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BackgroundOscillatory genes, with periodic expression at the mRNA and/or protein level, have been shown to play a pivotal role in many biological contexts. However, with the exception of the circadian clock and cell cycle, only a few such genes are known. Detecting oscillatory genes from snapshot single-cell experiments is a challenging task due to the lack of time information. Oscope is a recently proposed method to identify co-oscillatory gene pairs using single-cell RNA-seq data. Although promising, the current implementation of Oscope does not provide a principled statistical criterion for selecting oscillatory genes.ResultsWe improve the optimisation scheme underlying Oscope and provide a well-calibrated non-parametric hypothesis test to select oscillatory genes at a given FDR threshold. We evaluate performance on synthetic data and three real datasets and show that our approach is more sensitive than the original Oscope formulation, discovering larger sets of known oscillators while avoiding the need for less interpretable thresholds. We also describe how our proposed pseudo-time estimation method is more accurate in recovering the true cell order for each gene cluster while requiring substantially less computation time than the extended nearest insertion approach.ConclusionsOscoNet is a robust and versatile approach to detect oscillatory gene networks from snapshot single-cell data addressing many of the limitations of the original Oscope method.

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