Comprehensive study of tumour single nucleotide polymorphism array data reveals significant driver aberrations and disrupted signalling pathways in human hepatocellular cancer.

The authors describe an integrated method for analysing cancer driver aberrations and disrupted pathways by using tumour single nucleotide polymorphism (SNP) arrays. The authors new method adopts a novel statistical model to explicitly quantify the SNP signals, and therefore infers the genomic aberrations, including copy number alteration and loss of heterozygosity. Examination on the dilution series dataset shows that this method can correctly identify the genomic aberrations even with the existence of severe normal cell contamination in tumour sample. Furthermore, with the results of the aberration identification obtained from multiple tumour samples, a permutation-based approach is proposed for identifying the statistically significant driver aberrations, which are further incorporated with the known signalling pathways for pathway enrichment analysis. By applying the approach to 286 hepatocellular tumour samples, they successfully uncover numerous driver aberration regions across the cancer genome, for example, chromosomes 4p and 5q, which harbour many known hepatocellular cancer related genes such as alpha-fetoprotein (AFP) and ectodermal-neural cortex (ENC1). In addition, they identify nine disrupted pathways that are highly enriched by the driver aberrations, including the systemic lupus erythematosus pathway, the vascular endothelial growth factor (VEGF) signalling pathway and so on. These results support the feasibility and the utility of the proposed method on the characterisation of the cancer genome and the downstream analysis of the driver aberrations and the disrupted signalling pathways.

[Prediction of protein solvent accessibility with Markov chain model].

Residues in protein sequences can be classified into two (exposed / buried) or three (exposed/intermediate/buried) states according to their relative solvent accessibility. Markov chain model (MCM) had been adopted for statistical modeling and prediction. Different orders of MCM and classification thresholds were explored to find the best parameters. Prediction results for two different data sets and different cut-off thresholds were evaluated and compared with some existing methods, such as neural network, information theory and support vector machine. The best prediction accuracies achieved by the MCM method were 78.9% for the two-state prediction problem and 67.7% for the three-state prediction problem, respectively. A comprehensive comparison for all these results shows that the prediction accuracy and the correlative coefficient of the MCM method are better than or comparable to those obtained by the other prediction methods. At the same time, the advantage of this method is the lower computation complexity and better time-consuming performance.

PPSP: prediction of PK-specific phosphorylation site with Bayesian decision theory.

BACKGROUND: As a reversible and dynamic post-translational modification (PTM) of proteins, phosphorylation plays essential regulatory roles in a broad spectrum of the biological processes. Although many studies have been contributed on the molecular mechanism of phosphorylation dynamics, the intrinsic feature of substrates specificity is still elusive and remains to be delineated. RESULTS: In this work, we present a novel, versatile and comprehensive program, PPSP (Prediction of PK-specific Phosphorylation site), deployed with approach of Bayesian decision theory (BDT). PPSP could predict the potential phosphorylation sites accurately for approximately 70 PK (Protein Kinase) groups. Compared with four existing tools Scansite, NetPhosK, KinasePhos and GPS, PPSP is more accurate and powerful than these tools. Moreover, PPSP also provides the prediction for many novel PKs, say, TRK, mTOR, SyK and MET/RON, etc. The accuracy of these novel PKs are also satisfying. CONCLUSION: Taken together, we propose that PPSP could be a potentially powerful tool for the experimentalists who are focusing on phosphorylation substrates with their PK-specific sites identification. Moreover, the BDT strategy could also be a ubiquitous approach for PTMs, such as sumoylation and ubiquitination, etc.