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A biological function based biomarker panel optimization process.

ABSTRACT: Implementation of multi-gene biomarker panels identified from high throughput data, including microarray or next generation sequencing, need to be adapted to a platform suitable in a clinical setting such as quantitative polymerase chain reaction. However, technical challenges when transitioning from one measurement platform to another, such as inconsistent measurement results can affect panel development. We describe a process to overcome the challenges by replacing poor performing genes during platform transition and reducing the number of features without impacting classification performance. This approach assumes that a diagnostic panel reflects the effect of dysregulated biological processes associated with a disease, and genes involved in the same biological processes and coordinately affected by a disease share a similar discriminatory power. The utility of this optimization process was assessed using a published sepsis diagnostic panel. Substitution of more than half of the genes and/or reducing genes based on biological processes did not negatively affect the performance of the sepsis diagnostic panel. Our results suggest a systematic gene substitution and reduction process based on biological function can be used to alleviate the challenges associated with clinical development of biomarker panels.

SUBMITTER: Lee MY

PROVIDER: S-EPMC6517383 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A biological function based biomarker panel optimization process.

Lee Min Young MY Kim Taek-Kyun TK Walters Kathie-Anne KA Wang Kai K

Scientific reports 20190514 1

Implementation of multi-gene biomarker panels identified from high throughput data, including microarray or next generation sequencing, need to be adapted to a platform suitable in a clinical setting such as quantitative polymerase chain reaction. However, technical challenges when transitioning from one measurement platform to another, such as inconsistent measurement results can affect panel development. We describe a process to overcome the challenges by replacing poor performing genes during ...[more]

PMID: 31089177

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Project description:BackgroundThe identification of robust lists of molecular biomarkers related to a disease is a fundamental step for early diagnosis and treatment. However, methodologies for biomarker discovery using microarray data often provide results with limited overlap. It has been suggested that one reason for these inconsistencies may be that in complex diseases, such as cancer, multiple genes belonging to one or more physiological pathways are associated with the outcomes. Thus, a possible approach to improve list stability is to integrate biological information from genomic databases in the learning process; however, a comprehensive assessment based on different types of biological information is still lacking in the literature. In this work we have compared the effect of using different biological information in the learning process like functional annotations, protein-protein interactions and expression correlation among genes.ResultsBiological knowledge has been codified by means of gene similarity matrices and expression data linearly transformed in such a way that the more similar two features are, the more closely they are mapped. Two semantic similarity matrices, based on Biological Process and Molecular Function Gene Ontology annotation, and geodesic distance applied on protein-protein interaction networks, are the best performers in improving list stability maintaining almost equal prediction accuracy.ConclusionsThe performed analysis supports the idea that when some features are strongly correlated to each other, for example because are close in the protein-protein interaction network, then they might have similar importance and are equally relevant for the task at hand. Obtained results can be a starting point for additional experiments on combining similarity matrices in order to obtain even more stable lists of biomarkers. The implementation of the classification algorithm is available at the link: http://www.math.unipd.it/~dasan/biomarkers.html.

Dataset Information

A biological function based biomarker panel optimization process.

Publications

A biological function based biomarker panel optimization process.

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