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DOI: 10.4230/LIPIcs.WABI.2021.4
Perplexity: Evaluating Transcript Abundance Estimation in the Absence of Ground Truth

Authors: Jason Fan, Skylar Chan, and Rob Patro

Published in: LIPIcs, Volume 201, 21st International Workshop on Algorithms in Bioinformatics (WABI 2021)

Abstract
There has been rapid development of probabilistic models and inference methods for transcript abundance estimation from RNA-seq data. These models aim to accurately estimate transcript-level abundances, to account for different biases in the measurement process, and even to assess uncertainty in resulting estimates that can be propagated to subsequent analyses. The assumed accuracy of the estimates inferred by such methods underpin gene expression based analysis routinely carried out in the lab. Although hyperparameter selection is known to affect the distributions of inferred abundances (e.g. producing smooth versus sparse estimates), strategies for performing model selection in experimental data have been addressed informally at best. Thus, we derive perplexity for evaluating abundance estimates on fragment sets directly. We adapt perplexity from the analogous metric used to evaluate language and topic models and extend the metric to carefully account for corner cases unique to RNA-seq. In experimental data, estimates with the best perplexity also best correlate with qPCR measurements. In simulated data, perplexity is well behaved and concordant with genome-wide measurements against ground truth and differential expression analysis. To our knowledge, our study is the first to make possible model selection for transcript abundance estimation on experimental data in the absence of ground truth.
Cite as

Jason Fan, Skylar Chan, and Rob Patro. Perplexity: Evaluating Transcript Abundance Estimation in the Absence of Ground Truth. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 4:1-4:22, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)

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@InProceedings{fan_et_al:LIPIcs.WABI.2021.4,
  author =	{Fan, Jason and Chan, Skylar and Patro, Rob},
  title =	{{Perplexity: Evaluating Transcript Abundance Estimation in the Absence of Ground Truth}},
  booktitle =	{21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
  pages =	{4:1--4:22},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-200-6},
  ISSN =	{1868-8969},
  year =	{2021},
  volume =	{201},
  editor =	{Carbone, Alessandra and El-Kebir, Mohammed},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.4},
  URN =		{urn:nbn:de:0030-drops-143578},
  doi =		{10.4230/LIPIcs.WABI.2021.4},
  annote =	{Keywords: RNA-seq, transcript abundance estimation, model selection}
}
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