Apparent Bias Toward Long Gene Misregulation in MeCP2 Syndromes Disappears After Controlling for Baseline Variations

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Aug 15

PMID 30104565

Citations 24

Authors

Ayush T Raman

Amy E Pohodich

Ying-Wooi Wan

Hari Krishna Yalamanchili

William E Lowry

Huda Y Zoghbi

Zhandong Liu

Affiliations

Soon will be listed here.

Abstract

Recent studies have suggested that genes longer than 100 kb are more likely to be misregulated in neurological diseases associated with synaptic dysfunction, such as autism and Rett syndrome. These length-dependent transcriptional changes are modest in MeCP2-mutant samples, but, given the low sensitivity of high-throughput transcriptome profiling technology, here we re-evaluate the statistical significance of these results. We find that the apparent length-dependent trends previously observed in MeCP2 microarray and RNA-sequencing datasets disappear after estimating baseline variability from randomized control samples. This is particularly true for genes with low fold changes. We find no bias with NanoString technology, so this long gene bias seems to be particular to polymerase chain reaction amplification-based platforms. In contrast, authentic long gene effects, such as those caused by topoisomerase inhibition, can be detected even after adjustment for baseline variability. We conclude that accurate characterization of length-dependent (or other) trends requires establishing a baseline from randomized control samples.

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