Integrated analysis of transcript profiling and protein sequence data

Transcript profiling can be used to elucidate the molecular and cellular mechanisms involved in ageing and cancer. A recent study of human gastrointestinal stromal tumours (GISTs) with mutations in the KIT gene, Cancer Res. 61 (2001) 8624 exemplifies a common type of investigation. cDNA microarrays were used to generate measurements for 1987 clones in two types of tissues: 13 KIT mutation-positive GISTs and 6 spindle cell tumours from locations outside the gastrointestinal tract. Statistical problems associated with such two-class, high-dimensional profiling data include simultaneous classification and relevant feature identification, probabilistic clustering and protein sequence family modelling. Here, the GIST data were reexamined using specific solutions to these problems, namely sparse hyperplanes, nai;ve Bayes models and profile hidden Markov models respectively. The integrated analysis of molecular profiling and sequence data highlighted 6 clones that may be of clinical and experimental interest. The protein encoded by one of these putative biomarkers defined a novel protein family present in diverse eucarya. The family may be involved in chromosome segregation and/or stability. One family member is a potential biomarker identified recently from a retrospective analysis of transcript profiles for sporadic breast cancer samples from patients with poor and good prognosis, Signal Process. (in press).