CSAX: Characterizing Systematic Anomalies in eXpression Data
| Autor: | Andrea G. Edlow, Donna K. Slonim, Keith Noto, Heather C. Wick, Diana W. Bianchi, Saeed Majidi |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Blood Platelets Feature vector Datasets as Topic Sample (statistics) Computational biology Biology Bioinformatics Fetus Pregnancy Databases Genetic Genetics Humans Retinopathy of Prematurity Obesity Platelet activation Molecular Biology Research Articles Gene Expression Profiling Infant Newborn Amniotic Fluid Platelet Activation Expression (mathematics) Gene expression profiling Oxidative Stress Computational Mathematics Phenotype Computational Theory and Mathematics Pregnancy Trimester Second Modeling and Simulation Female Anomaly detection Transcriptome Algorithms Software Curse of dimensionality |
| Zdroj: | Journal of Computational Biology |
| ISSN: | 1557-8666 1066-5277 |
| DOI: | 10.1089/cmb.2014.0155 |
| Popis: | Methods for translating gene expression signatures into clinically relevant information have typically relied upon having many samples from patients with similar molecular phenotypes. Here, we address the question of what can be done when it is relatively easy to obtain healthy patient samples, but when abnormalities corresponding to disease states may be rare and one-of-a-kind. The associated computational challenge, anomaly detection, is a well-studied machine-learning problem. However, due to the dimensionality and variability of expression data, existing methods based on feature space analysis or individual anomalously expressed genes are insufficient. We present a novel approach, CSAX, that identifies pathways in an individual sample in which the normal expression relationships are disrupted. To evaluate our approach, we have compiled and released a compendium of public expression data sets, reformulated to create a test bed for anomaly detection. We demonstrate the accuracy of CSAX on the data sets in our compendium, compare it to other leading methods, and show that CSAX aids in both identifying anomalies and explaining their underlying biology. We describe an approach to characterizing the difficulty of specific expression anomaly detection tasks. We then illustrate CSAX's value in two developmental case studies. Confirming prior hypotheses, CSAX highlights disruption of platelet activation pathways in a neonate with retinopathy of prematurity and identifies, for the first time, dysregulated oxidative stress response in second trimester amniotic fluid of fetuses with obese mothers. Our approach provides an important step toward identification of individual disease patterns in the era of precision medicine. |
| Databáze: | OpenAIRE |
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