Identifying subgroup markers in heterogeneous populations.
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.
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, Division of Molecular Biology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, Division of Medical Oncology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands and Faculty of EEMCS, Delft University of Technology, 2628 CN, Delft, The Netherlands.
Jorma J
JJ
de Ronde
Guillem
G
Rigaill
Sven
S
Rottenberg
Sjoerd
S
Rodenhuis
Lodewyk F A
LF
Wessels
D000465:Algorithms; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases