Reply to "Issues arising from benchmarking single-cell RNA sequencing imputation methods"

TL;DR

This paper defends the validity of a data downsampling experiment used to evaluate imputation methods for single-cell RNA sequencing, addressing concerns raised about the experimental design and results.

Contribution

It clarifies and amends the previous downsampling experiment to confirm the robustness of the original findings in single-cell RNA imputation evaluation.

Findings

The original downsampling results are validated.

SAVER performs comparably to MAGIC and scImpute.

The experimental approach is robust and reliable.

Abstract

In our Brief Communication (DOI: 10.1038/s41592-018-0033-z), we presented the method SAVER for recovering true gene expression levels in noisy single cell RNA sequencing data. We evaluated the performance of SAVER, along with comparable methods MAGIC and scImpute, in an RNA FISH validation experiment and a data downsampling experiment. In a Comment [arXiv:1908.07084v1], Li & Li were concerned with the use of the downsampled datasets, specifically focusing on clustering results obtained from the Zeisel et al. data. Here, we will address these comments and, furthermore, amend the data downsampling experiment to demonstrate that the findings from the data downsampling experiment in our Brief Communication are valid.