Integration of multi-omics data for prediction of phenotypic traits using random forest
Open accessAbstract
BACKGROUND: In order to find genetic and metabolic pathways related to phenotypic traits of interest, we analyzed gene expression data, metabolite data obtained with GC-MS and LC-MS, proteomics data and a selected set of tuber quality phenotypic data from a diploid segregating mapping population of potato. In this study we present an approach to integrate these ~ omics data sets for the purpose of predicting phenotypic traits. This gives us networks of relatively small sets of interrelated ~ omics variables that can predict, with higher accuracy, a quality trait of interest. RESULTS: We used Random Forest regression for integrating multiple ~ omics data for prediction of four quality traits of potato: tuber flesh colour, DSC onset, tuber shape and enzymatic discoloration. For tuber flesh colour beta-carotene hydroxylase and zeaxanthin epoxidase were ranked first and forty-fourth respectively both of which have previously been associated with flesh colour in potato tubers. Combining all the significant genes, LC-peaks, GC-peaks and proteins, the variation explained was 75 %, only slightly more than what gene expression or LC-MS data explain by themselves which indicates that there are correlations among the variables across data sets. For tuber shape regressed on the gene expression, LC-MS, GC-MS and proteomics data sets separately, only gene expression data was found to explain significant variation. For DSC onset, we found 12 significant gene expression, 5 metabolite levels (GC) and 2 proteins that are associated with the trait. Using those 19 significant variables, the variation explained was 45 %. Expression QTL (eQTL) analyses showed many associations with genomic regions in chromosome 2 with also the highest explained variation compared to other chromosomes. Transcriptomics and metabolomics analysis on enzymatic discoloration after 5 min resulted in 420 significant genes and 8 significant LC metabolites, among which two were putatively identified as caffeoylquinic acid methyl ester and tyrosine. CONCLUSIONS: In this study, we made a strategy for selecting and integrating multiple ~ omics data using random forest method and selected representative individual peaks for networks based on eQTL, mQTL or pQTL information. Network analysis was done to interpret how a particular trait is associated with gene expression, metabolite and protein data.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Multi-omics studies have been successfully conducted in plants and animals.
“Multi-omics studies have also been successfully conducted in plants (potato (Acharjee et al., 2016(Acharjee et al., , 2011))) and animals (such as canine heart disease (Li et al., 2015)).”
From Using machine learning approaches for multi-omics data analysis: A review (2021) · cites this paper as Acharjee et al., 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Breiman, L. (2001) · Machine Learning · doi:10.1023/a:1010933404324 · Cited by 133,538 · see citing works
The Elements of Statistical Learning
Hastie, T., Tibshirani, R., & Friedman, J. (2009) · Springer Series in Statistics · doi:10.1007/978-0-387-84858-7 · Cited by 25,970 · see citing works
The Elements of Statistical Learning
Hastie, T., Friedman, J., & Tibshirani, R. (2001) · Springer Series in Statistics · doi:10.1007/978-0-387-21606-5 · Cited by 24,162 · see citing works
Mass spectrometry-based proteomics
Aebersold, R., & Mann, M. (2003) · Nature · doi:10.1038/nature01511 · Cited by 6,955 · see citing works
Metabolomics—the link between genotypes and phenotypes
Fiehn, O. (2002) · Plant Molecular Biology · doi:10.1023/a:1013713905833 · Cited by 3,445 · see citing works
Metabolomics — the link between genotypes and phenotypes
Fiehn, O. (2002) · Springer eBooks · doi:10.1007/978-94-010-0448-0_11 · Cited by 3,168 · see citing works
Genome sequence and analysis of the tuber crop potato
Xu, X., Pan, S., Cheng, S., Zhang, B., Mu, D., Ni, P., Zhang, G., Guzman, F., Torres, M., Lozano, R., et al. (2011) · Nature · doi:10.1038/nature10158 · Cited by 2,050 · see citing works
Self-citationMetabolomics--the link between genotypes and phenotypes.
Fiehn, O. (2002) · PubMed · Cited by 1,517 · see citing works
Genetical genomics: the added value from segregation
Jansen, R. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02310-1 · Cited by 1,010 · see citing works
Measuring the metabolome: current analytical technologies
Dunn, W. B., Bailey, N. J. C., & Johnson, H. E. (2005) · The Analyst · doi:10.1039/b418288j · Cited by 922 · see citing works
Bachem, C., van der Hoeven, R. S., de Bruijn, S. M., Vreugdenhil, D., Zabeau, M., & Visser, R. G. F. (1996) · The Plant Journal · doi:10.1046/j.1365-313x.1996.9050745.x · Cited by 853 · see citing works
Self-citationBrāzma, A., & Vilo, J. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01772-5 · Cited by 602 · see citing works
Discovery of meaningful associations in genomic data using partial correlation coefficients
de la Fuente, A., Bing, N., Hoeschele, I., & Mendes, P. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth445 · Cited by 552 · see citing works
The genetics of plant metabolism
Keurentjes, J. J. B., Fu, J., de Vos, C. H. R., Lommen, A., Hall, R. D., Bino, R. J., van der Plas, L. H. W., Jansen, R. C., Vreugdenhil, D., & Koornneef, M. (2006) · Nature Genetics · doi:10.1038/ng1815 · Cited by 499 · see citing works
Zhu, H., Bilgin, M., & Snyder, M. P. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161511 · Cited by 331 · see citing works
Integrated omics approaches in plant systems biology
Fukushima, A., Kusano, M., Redestig, H., Arita, M., & Saito, K. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.09.022 · Cited by 243 · see citing works
Tikunov, Y. M., Laptenok, S. P., Hall, R. D., et al. (2011) · Metabolomics · doi:10.1007/s11306-011-0368-2 · Cited by 237 · see citing works
Regularized estimation of large-scale gene association networks using graphical Gaussian models
Krämer, N., Schäfer, J., & Boulesteix, A. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-384 · Cited by 236 · see citing works
Ruiz, D., & Egea, J. A. (2007) · Euphytica · doi:10.1007/s10681-007-9640-y · Cited by 230 · see citing works
Exploring and exploiting carotenoid accumulation in Dunaliella salina for cell-factory applications
Lamers, P. P., Janssen, M. G. J., de Vos, R. C. H., Bino, R. J., & Wijffels, R. H. (2008) · Trends in biotechnology · doi:10.1016/j.tibtech.2008.07.002 · Cited by 222 · see citing works
Plant systems biology comes of age
Yuan, J. S., Galbraith, D. W., Dai, S. Y., Griffin, P. R., & Stewart, C. N. (2008) · Trends in Plant Science · doi:10.1016/j.tplants.2008.02.003 · Cited by 183 · see citing works
Jacobs, J. M. E., van Eck, H. J., Arens, P. F. P., et al. (1995) · Theoretical and Applied Genetics · doi:10.1007/bf00220891 · Cited by 162 · see citing works
van Eck, H. J., Jacobs, J. M. E., Stam, P., et al. (1994) · Genetics · doi:10.1093/genetics/137.1.303 · Cited by 157 · see citing works
Carreño-Quintero, N., Acharjee, A., Maliepaard, C. A., Bachem, C., Mumm, R., Bouwmeester, H. J., Visser, R. G. F., & Keurentjes, J. J. B. (2012) · PLANT PHYSIOLOGY · doi:10.1104/pp.111.188441 · Cited by 150 · see citing works
Self-citationKloosterman, B., Koeyer, D. L. D., Griffiths, R., Flinn, B. S., Steuernagel, B., Scholz, U., Sonnewald, S., Sonnewald, U., Bryan, G. J., Prat, S., et al. (2008) · Functional & Integrative Genomics · doi:10.1007/s10142-008-0083-x · Cited by 136 · see citing works
Self-citationDiscovering plant metabolic biomarkers for phenotype prediction using an untargeted approach
Steinfath, M., Strehmel, N., Peters, R., et al. (2010) · Plant Biotechnology Journal · doi:10.1111/j.1467-7652.2010.00516.x · Cited by 132 · see citing works
Wolters, A. A., Uitdewilligen, J. G. A. M. L., Kloosterman, B., Hutten, R. C. B., Visser, R. G. F., & van Eck, H. J. (2010) · Plant Molecular Biology · doi:10.1007/s11103-010-9647-y · Cited by 107 · see citing works
Self-citationAcharjee, A., Kloosterman, B., de Vos, R. C. H., et al. (2011) · Analytica Chimica Acta · doi:10.1016/j.aca.2011.03.050 · Cited by 95 · see citing works
Self-citationBrown, C. R., Kim, T. S., Ganga, Z., et al. (2006) · American Journal of Potato Research · doi:10.1007/bf02872013 · Cited by 86 · see citing works
Kloosterman, B., Oortwijn, M. E. P., Uitdewilligen, J. G. A. M. L., et al. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-158 · Cited by 84 · see citing works
Self-citationMaking the most of microarray data
Gaasterland, T., & Bekiranov, S. (2000) · Nature Genetics · doi:10.1038/73392 · Cited by 71 · see citing works
Werij, J. S., Kloosterman, B., Celis-Gamboa, C., et al. (2007) · Theoretical and Applied Genetics · doi:10.1007/s00122-007-0560-y · Cited by 67 · see citing works
Self-citationIntegrated network analysis and effective tools in plant systems biology
Fukushima, A., Kanaya, S., & Nishida, K. (2014) · Frontiers in Plant Science · doi:10.3389/fpls.2014.00598 · Cited by 59 · see citing works
Differential scanning calorimetry and a model calculation of starches annealed at 20 and 50°C
Kohyama, K., & Sasaki, T. (2005) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2005.08.004 · Cited by 54 · see citing works
Data integration and analysis of biological networks
Kim, T. Y., Kim, H. U., & Lee, S. Y. (2010) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2010.01.003 · Cited by 46 · see citing works
Celis-Gamboa, C., Struik, P. C., Jacobsen, E., et al. (2003) · Annals of Applied Biology · doi:10.1111/j.1744-7348.2003.tb00284.x · Cited by 46 · see citing works
Finding Associations among Histone Modifications Using Sparse Partial Correlation Networks
Lasserre, J., Chung, H., & Vingron, M. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003168 · Cited by 44 · see citing works
Biological network inference using low order partial correlation
Zuo, Y., Yu, G., Tadesse, M. G., et al. (2014) · Methods · doi:10.1016/j.ymeth.2014.06.010 · Cited by 42 · see citing works
The life cycle of the potato (Solanum tuberosum L.) : from crop physiology to genetics
Celis-Gamboa, B. C. (2002) · doi:10.18174/199013 · Cited by 39 · see citing works
Bachem, C., Horváth, B. M., Trindade, L. M., et al. (2001) · The Plant Journal · doi:10.1046/j.1365-313x.2001.00993.x · Cited by 37 · see citing works
MetaNetwork: a computational protocol for the genetic study of metabolic networks
Fu, J., Swertz, M. A., Keurentjes, J. J. B., et al. (2007) · Nature Protocols · doi:10.1038/nprot.2007.96 · Cited by 35 · see citing works
Kloosterman, B., Anithakumari, A. M., Chibon, P., et al. (2012) · BMC Plant Biology · doi:10.1186/1471-2229-12-17 · Cited by 20 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Using machine learning approaches for multi-omics data analysis: A review
Reel, P. S., Reel, S., Pearson, E., Trucco, E., & Jefferson, E. (2021) · Biotechnology Advances · doi:10.1016/j.biotechadv.2021.107739 · Cited by 903 · see citing works
Multi-omics revolution to promote plant breeding efficiency
Mahmood, U., Li, X., Fan, Y., Chang, W., Niu, Y., Li, J., Qu, C., & Lu, K. (2022) · Frontiers in Plant Science · doi:10.3389/fpls.2022.1062952 · Cited by 145 · see citing works
Multi-omics integration strategies for animal epigenetic studies — A review
Kim, D.-Y., & Kim, J.-M. (2021) · Animal Bioscience · doi:10.5713/ab.21.0042 · Cited by 47 · see citing works
- Authors
- Acharjee, A., Kloosterman, B., Visser, R. G. F., & Maliepaard, C.
- Affiliations
- MRC Elsie Widdowson Laboratory (GB)
- KeyGene (Netherlands) (NL)
- Wageningen University & Research (NL)
- Corresponding author
- Maliepaard, Chris
- Venue
- BMC Bioinformatics
- Published
- 2016-06
- Volume
- 17
- Issue
- S5
- Pages
- 180-180
- ISSN
- 1471-2105 (ISSN-L)
- PMC
- PMC4905610
- OpenAlex
- W2418706671
- Cited by
- 109
- References
- 42
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 15 · 2020: 13 · 2019: 10 · 2018: 5 · 2017: 7 · 2016: 3
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Bioinformatics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- multi-omics integration, potato tuber quality, phenotype prediction, tuber shape, gene expression, metabolomics, proteomics, expression QTL, β-carotene hydroxylase, zeaxanthin epoxidase, tyrosine, random forest regression, network analysis
- MeSH terms
- Chromatography, High Pressure Liquid, Gas Chromatography-Mass Spectrometry, Phenotype, Plant Proteins, Solanum tuberosum, Mass Spectrometry, Gene Expression Regulation, Plant, Genomics, Chromosomes, Plant, Plant Tubers, Quantitative Trait Loci, Proteomics, Metabolomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review