Identifying subgroup markers in heterogeneous populations

Identifying subgroup markers in heterogeneous populations

De Ronde, J.J.
Rigaill, G.
Rottenberg, S.
Rodenhuis, S.
Wessels, L.F.A.

Electrical Engineering, Mathematics and Computer Science

Intelligent Systems

2013-09-22

Traditional methods that aim to identify biomarkers that distinguish between two groups, like Significance Analysis of Microarrays or the t-test, perform optimally when such biomarkers show homogeneous behavior within each group and differential behavior between the groups. However, in many applications, this is not the case. Instead, a subgroup of samples in one group shows differential behavior with respect to all other samples. To successfully detect markers showing such imbalanced patterns of differential signal, a different approach is required. We propose a novel method, specifically designed for the Detection of Imbalanced Differential Signal (DIDS). We use an artificial dataset and a human breast cancer dataset to measure its performance and compare it with three traditional methods and four approaches that take imbalanced signal into account. Supported by extensive experimental results, we show that DIDS outperforms all other approaches in terms of power and positive predictive value. In a mouse breast cancer dataset, DIDS is the only approach that detects a functionally validated marker of chemotherapy resistance. DIDS can be applied to any continuous value data, including gene expression data, and in any context where imbalanced differential signal is manifested.

http://resolver.tudelft.nl/uuid:b99c5aad-0a44-4e49-bdd5-5f0338bf01c5

https://doi.org/10.1093/nar/gkt845

Oxford University Press

0305-1048

Nucleic Acids Research, 41 (21), 2013

Institutional Repository

journal article

(c) 2013 The Author(s)
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