RADAR: differential analysis of MeRIP-seq data with a random effect model

Zijie Zhang; Qi Zhan; Mark Eckert; Allen Zhu; Agnieszka Chryplewicz; Dario F De Jesus; Decheng Ren; Rohit N Kulkarni; Ernst Lengyel; Chuan He; Mengjie Chen

doi:10.1186/s13059-019-1915-9

RADAR: differential analysis of MeRIP-seq data with a random effect model

Genome Biol. 2019 Dec 23;20(1):294. doi: 10.1186/s13059-019-1915-9.

Authors

Zijie Zhang^{1

2

3}, Qi Zhan^{4

5}, Mark Eckert⁶, Allen Zhu^{1

2

3}, Agnieszka Chryplewicz⁶, Dario F De Jesus⁷, Decheng Ren⁸, Rohit N Kulkarni⁷, Ernst Lengyel⁶, Chuan He^{9

10

11}, Mengjie Chen^{12

13}

Affiliations

¹ Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, 60637, USA.
² Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, 60637, USA.
³ Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, 60637, USA.
⁴ Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
⁵ Department of Human Genetics, The University of Chicago, Chicago, IL, 60637, USA.
⁶ Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Chicago, Chicago, IL, 60637, USA.
⁷ Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center and Harvard Medical School, Boston, MA, 02215, USA.
⁸ Section of Endocrinology, Diabetes & Metabolism, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
⁹ Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, 60637, USA. chuanhe@uchicago.edu.
¹⁰ Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, 60637, USA. chuanhe@uchicago.edu.
¹¹ Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, 60637, USA. chuanhe@uchicago.edu.
¹² Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA. mengjiechen@uchicago.edu.
¹³ Department of Human Genetics, The University of Chicago, Chicago, IL, 60637, USA. mengjiechen@uchicago.edu.

Abstract

Epitranscriptome profiling using MeRIP-seq is a powerful technique for in vivo functional studies of reversible RNA modifications. We develop RADAR, a comprehensive analytical tool for detecting differentially methylated loci in MeRIP-seq data. RADAR enables accurate identification of altered methylation sites by accommodating variability of pre-immunoprecipitation expression level and post-immunoprecipitation count using different strategies. In addition, it is compatible with complex study design when covariates need to be incorporated in the analysis. Through simulation and real dataset analyses, we show that RADAR leads to more accurate and reproducible differential methylation analysis results than alternatives, which is available at https://github.com/scottzijiezhang/RADAR.

Keywords: Differential methylation; MeRIP-seq; N6-adenosine methylation (m6A).

Publication types

Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Animals
Humans
Immunoprecipitation
Methylation
Mice, Knockout
Models, Statistical*
Sequence Analysis, RNA*
Software*

Abstract

Publication types

MeSH terms

Grants and funding