RNAAgeCalc: A multi-tissue transcriptional age calculator

被引:46
作者
Ren, Xu [1 ]
Kuan, Pei Fen [1 ]
机构
[1] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA
关键词
DNA METHYLATION; GENE; PROFILES; CANCER; REGULARIZATION; METAANALYSIS; RISK;
D O I
10.1371/journal.pone.0237006
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Biological aging reflects decline in physiological functions and is an effective indicator of morbidity and mortality. Numerous epigenetic age calculators are available, however biological aging calculators based on transcription remain scarce. Here, we introduce RNAAgeCalc, a versatile across-tissue and tissue-specific transcriptional age calculator. By performing a meta-analysis of transcriptional age signature across multi-tissues using the GTEx database, we identify 1,616 common age-related genes, as well as tissue-specific age-related genes. Based on these genes, we develop new across-tissue and tissue-specific age predictors. We show that our transcriptional age calculator outperforms other prior age related gene signatures as indicated by the higher correlation with chronological age as well as lower median and median error. Our results also indicate that both racial and tissue differences are associated with transcriptional age. Furthermore, we demonstrate that the transcriptional age acceleration computed from our within-tissue predictor is significantly correlated with mutation burden, mortality risk and cancer stage in several types of cancer from the TCGA database, and offers complementary information to DNA methylation age. RNAAgeCalc is available at http://www.ams.sunysb.edu/similar to pfkuan/softwares.html#RNAAgeCalc, both as Bioconductor and Python packages, accompanied by a user-friendly interactive Shiny app.
引用
收藏
页数:21
相关论文
共 47 条
[1]   Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species [J].
Anastasiadi, Dafni ;
Esteve-Codina, Anna ;
Piferrer, Francesc .
EPIGENETICS & CHROMATIN, 2018, 11
[2]  
[Anonymous], **DATA OBJECT**
[3]  
[Anonymous], 2018, ORG HS EG DB GENOME
[4]  
[Anonymous], **DATA OBJECT**
[5]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[6]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[7]   Random forests [J].
Breiman, L .
MACHINE LEARNING, 2001, 45 (01) :5-32
[8]   Random forests [J].
Breiman, L .
MACHINE LEARNING, 2001, 45 (01) :5-32
[9]   Reproducible RNA-seq analysis using recount2 [J].
Collado-Torres, Leonardo ;
Nellore, Abhinav ;
Kammers, Kai ;
Ellis, Shannon E. ;
Taub, Margaret A. ;
Hansen, Kasper D. ;
Jaffe, Andrew E. ;
Langmead, Ben ;
Leek, Jeffrey T. .
NATURE BIOTECHNOLOGY, 2017, 35 (04) :319-321
[10]   SUPPORT-VECTOR NETWORKS [J].
CORTES, C ;
VAPNIK, V .
MACHINE LEARNING, 1995, 20 (03) :273-297