Format

Send to

Choose Destination
Genome Biol. 2015 Jun 25;16:133. doi: 10.1186/s13059-015-0694-1.

Comparison of RNA-seq and microarray-based models for clinical endpoint prediction.

Author information

1
BGI-Shenzhen, Main Building, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, 518083, China.
2
Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and School of Pharmacy, Fudan University, Shanghai, 201203, China.
3
Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Kerpener Strasse 62, D-50924, Cologne, Germany.
4
University of Cologne, Center for Molecular Medicine (CMMC), Medical Faculty, Kerpener Strasse 62, D-50924, Cologne, Germany.
5
NIH/NCBI, Bldg 38A/Room 8S808, 8600 Rockville Pike, Bethesda, MD, 20894, USA.
6
Eli Lilly and Company Research Informatics, Lilly Corporate Center, Drop Code 0725, Indianapolis, IN, 46285, USA.
7
Fondazione Bruno Kessler (FBK), Via Sommarive 18, 38123, Trento Povo, TN, Italy.
8
AbbVie Inc., Global Pharmaceutical R&D, 32 Knights Crest Court, Souderton, PA, 18964, USA.
9
GlaxoSmithKline, Discovery Analytics, Mailstop UP4335, 1250 South Collegeville Rd, Collegeville, PA, 19426, USA.
10
Department of Internal Medicine, Rush University Cancer Center, 1725 W. Harrison Street, Chicago, IL, 60612, USA.
11
National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, 72079, USA.
12
SAS Institute Inc., SAS Campus Drive, Cary, NC, 27513, USA.
13
Marshfield Clinic Research Foundation, Biomedical Informatics Research Center, 1000 N Oak Avenue, Marshfield, WI, 54449, USA.
14
Thomson Reuters IP & Science, 5901 Priesty Drive, Carlsbad, CA, 92008, USA.
15
Center for Genomics and Division of Microbiology & Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, CA, 92350, USA.
16
Department of Biomedical Engineering, GeorgiaTech and Emory University, 313 Ferst Drive, Atlanta, GA, 30332, USA.
17
Fondazione Edmund Mach, CRI-CBC, San Michele all'Adige, TN, Italy.
18
Children's Hospital Los Angeles, Los Angeles, CA, 90027, USA.
19
Department of Pediatric Hematology-Oncology, Molecular Oncology, Felsenstein Medical Research Center, Schneider Children's Medical Center of Israel, Petach Tikva, 49202, Israel.
20
Marshfield Clinic Research Foundation, Center of Human Genetics, 1000 N Oak Avenue, Marshfield, WI, 54449, USA.
21
Department of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany.
22
University of Nottingham, Children's Brain Tumour Research Centre, Queen's Medical Centre, University of Nottingham, D Floor Medical School, Nottingham, NG7 2UH, UK.
23
Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, WOC1 RM400S, HFM-210, 1401 Rockville Pike, Rockville, MD, 20852, USA.
24
AbbVie Inc., Global Pharmaceutical Research and Development, 1 North Waukegan Road, North Chicago, IL, 60064, USA.
25
University of Arkansas at Little Rock, UALR/UAMS Joint Bioinformatics Graduate Program, 2801 South University Avenue, Little Rock, AR, 72204, USA.
26
Eli Lilly and Company, Discovery Statistics, Lilly Corporate Center, Drop Code 2036, Indianapolis, IN, 46285, USA.
27
Department of Pathology, University of Valencia, Medical School, Avda. Blasco Ibáñez, 17, 46010, Valencia, Spain.
28
Department of Translational Genomics, University of Cologne, D-50924, Cologne, Germany.
29
Neuroblastoma Laboratory, Onco/Hematology Laboratory, SDB Department, University of Padua, Pediatric Research Institute, Padua, Italy.
30
Department of Pediatrics and Genetics, Ghent University, Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
31
Georgia Institute of Technology, School of Electrical and Computer Engineering, 777 Atlantic Drive NW, Atlanta, GA, 30332, USA.
32
Harvard Medical School, Massachusetts General Hospital, 51 Blossom Street, Boston, MA, 02114, USA.
33
Stanford University, Stanford Genome Technology Center, 855 South California Avenue, Palo Alto, CA, 94304, USA.
34
Department of Pathology, University of North Dakota School of Medicine, 501 N. Columbia Road RM 3573, Grand Forks, ND, 58202-9037, USA.
35
East China Normal University, Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, 500 Dongchuan Road, Shanghai, 200241, China.
36
Department of Molecular & Cellular Biology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010, USA.
37
Department of Biology, University of Copenhagen, Copenhagen, DK-2200, Denmark.
38
King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
39
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DK-2200, Denmark.
40
Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and School of Pharmacy, Fudan University, Shanghai, 201203, China. lemingshi@fudan.edu.cn.
41
National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, 72079, USA. lemingshi@fudan.edu.cn.
42
BGI-Shenzhen, Main Building, Bei Shan Industrial Zone, Yantian District, Shenzhen, Guangdong, 518083, China. pengzhiyu@genomics.org.cn.
43
BGI-Guangzhou, Guangzhou Higher Education Mega Center, No. 280, Waihuan East Rd., Guangzhou, 510006, China. pengzhiyu@genomics.org.cn.
44
Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Kerpener Strasse 62, D-50924, Cologne, Germany. matthias.fischer@uk-koeln.de.
45
University of Cologne, Center for Molecular Medicine (CMMC), Medical Faculty, Kerpener Strasse 62, D-50924, Cologne, Germany. matthias.fischer@uk-koeln.de.

Abstract

BACKGROUND:

Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model.

RESULTS:

We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models.

CONCLUSIONS:

We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

PMID:
26109056
PMCID:
PMC4506430
DOI:
10.1186/s13059-015-0694-1
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center