An ontology-based method for assessing batch effect adjustment approaches in heterogeneous datasets

Florian Schmidt, Markus List, Engin Cukuroglu, Sebastian Köhler, Jonathan Göke, Marcel H. Schulz

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Motivation International consortia such as the Genotype-Tissue Expression (GTEx) project, The Cancer Genome Atlas (TCGA) or the International Human Epigenetics Consortium (IHEC) have produced a wealth of genomic datasets with the goal of advancing our understanding of cell differentiation and disease mechanisms. However, utilizing all of these data effectively through integrative analysis is hampered by batch effects, large cell type heterogeneity and low replicate numbers. To study if batch effects across datasets can be observed and adjusted for, we analyze RNA-seq data of 215 samples from ENCODE, Roadmap, BLUEPRINT and DEEP as well as 1336 samples from GTEx and TCGA. While batch effects are a considerable issue, it is non-trivial to determine if batch adjustment leads to an improvement in data quality, especially in cases of low replicate numbers. Results We present a novel method for assessing the performance of batch effect adjustment methods on heterogeneous data. Our method borrows information from the Cell Ontology to establish if batch adjustment leads to a better agreement between observed pairwise similarity and similarity of cell types inferred from the ontology. A comparison of state-of-the art batch effect adjustment methods suggests that batch effects in heterogeneous datasets with low replicate numbers cannot be adequately adjusted. Better methods need to be developed, which can be assessed objectively in the framework presented here. Availability and implementation Our method is available online at https://github.com/SchulzLab/OntologyEval. Supplementary information Supplementary data are available at Bioinformatics online.

Original languageEnglish
Pages (from-to)i908-i916
JournalBioinformatics
Volume34
Issue number17
DOIs
StatePublished - 1 Sep 2018

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