Dataset Information

Multiple-kernel learning for genomic data mining and prediction.

ABSTRACT:

Background

Advances in medical technology have allowed for customized prognosis, diagnosis, and treatment regimens that utilize multiple heterogeneous data sources. Multiple kernel learning (MKL) is well suited for the integration of multiple high throughput data sources. MKL remains to be under-utilized by genomic researchers partly due to the lack of unified guidelines for its use, and benchmark genomic datasets.

Results

We provide three implementations of MKL in R. These methods are applied to simulated data to illustrate that MKL can select appropriate models. We also apply MKL to combine clinical information with miRNA gene expression data of ovarian cancer study into a single analysis. Lastly, we show that MKL can identify gene sets that are known to play a role in the prognostic prediction of 15 cancer types using gene expression data from The Cancer Genome Atlas, as well as, identify new gene sets for the future research.

Conclusion

Multiple kernel learning coupled with modern optimization techniques provides a promising learning tool for building predictive models based on multi-source genomic data. MKL also provides an automated scheme for kernel prioritization and parameter tuning. The methods used in the paper are implemented as an R package called RMKL package, which is freely available for download through CRAN at https://CRAN.R-project.org/package=RMKL .

SUBMITTER: Wilson CM

PROVIDER: S-EPMC6694479 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Multiple-kernel learning for genomic data mining and prediction.

Wilson Christopher M CM Li Kaiqiao K Yu Xiaoqing X Kuan Pei-Fen PF Wang Xuefeng X

BMC bioinformatics 20190815 1

<h4>Background</h4>Advances in medical technology have allowed for customized prognosis, diagnosis, and treatment regimens that utilize multiple heterogeneous data sources. Multiple kernel learning (MKL) is well suited for the integration of multiple high throughput data sources. MKL remains to be under-utilized by genomic researchers partly due to the lack of unified guidelines for its use, and benchmark genomic datasets.<h4>Results</h4>We provide three implementations of MKL in R. These method ...[more]

PMID: 31416413

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Project description:BackgroundIdentification of molecular mechanisms that determine tumour progression in cancer patients is a prerequisite for developing new disease treatment guidelines. Even though the predictive performance of current machine learning models is promising, extracting significant and meaningful knowledge from the data simultaneously during the learning process is a difficult task considering the high-dimensional and highly correlated nature of genomic datasets. Thus, there is a need for models that not only predict tumour volume from gene expression data of patients but also use prior information coming from pathway/gene sets during the learning process, to distinguish molecular mechanisms which play crucial role in tumour progression and therefore, disease prognosis.ResultsIn this study, instead of initially choosing several pathways/gene sets from an available set and training a model on this previously chosen subset of genomic features, we built a novel machine learning algorithm, PrognosiT, that accomplishes both tasks together. We tested our algorithm on thyroid carcinoma patients using gene expression profiles and cancer-specific pathways/gene sets. Predictive performance of our novel multiple kernel learning algorithm (PrognosiT) was comparable or even better than random forest (RF) and support vector regression (SVR). It is also notable that, to predict tumour volume, PrognosiT used gene expression features less than one-tenth of what RF and SVR algorithms used.ConclusionsPrognosiT was able to obtain comparable or even better predictive performance than SVR and RF. Moreover, we demonstrated that during the learning process, our algorithm managed to extract relevant and meaningful pathway/gene sets information related to the studied cancer type, which provides insights about its progression and aggressiveness. We also compared gene expressions of the selected genes by our algorithm in tumour and normal tissues, and we then discussed up- and down-regulated genes selected by our algorithm while learning, which could be beneficial for determining new biomarkers.

Project description:BACKGROUND: This paper introduces the notion of optimizing different norms in the dual problem of support vector machines with multiple kernels. The selection of norms yields different extensions of multiple kernel learning (MKL) such as L(infinity), L1, and L2 MKL. In particular, L2 MKL is a novel method that leads to non-sparse optimal kernel coefficients, which is different from the sparse kernel coefficients optimized by the existing L(infinity) MKL method. In real biomedical applications, L2 MKL may have more advantages over sparse integration method for thoroughly combining complementary information in heterogeneous data sources. RESULTS: We provide a theoretical analysis of the relationship between the L2 optimization of kernels in the dual problem with the L2 coefficient regularization in the primal problem. Understanding the dual L2 problem grants a unified view on MKL and enables us to extend the L2 method to a wide range of machine learning problems. We implement L2 MKL for ranking and classification problems and compare its performance with the sparse L(infinity) and the averaging L1 MKL methods. The experiments are carried out on six real biomedical data sets and two large scale UCI data sets. L2 MKL yields better performance on most of the benchmark data sets. In particular, we propose a novel L2 MKL least squares support vector machine (LSSVM) algorithm, which is shown to be an efficient and promising classifier for large scale data sets processing. CONCLUSIONS: This paper extends the statistical framework of genomic data fusion based on MKL. Allowing non-sparse weights on the data sources is an attractive option in settings where we believe most data sources to be relevant to the problem at hand and want to avoid a "winner-takes-all" effect seen in L(infinity) MKL, which can be detrimental to the performance in prospective studies. The notion of optimizing L2 kernels can be straightforwardly extended to ranking, classification, regression, and clustering algorithms. To tackle the computational burden of MKL, this paper proposes several novel LSSVM based MKL algorithms. Systematic comparison on real data sets shows that LSSVM MKL has comparable performance as the conventional SVM MKL algorithms. Moreover, large scale numerical experiments indicate that when cast as semi-infinite programming, LSSVM MKL can be solved more efficiently than SVM MKL. AVAILABILITY: The MATLAB code of algorithms implemented in this paper is downloadable from http://homes.esat.kuleuven.be/~sistawww/bioi/syu/l2lssvm.html.

Dataset Information

Multiple-kernel learning for genomic data mining and prediction.

Background

Results

Conclusion

Publications

Multiple-kernel learning for genomic data mining and prediction.

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