Mingguang Shi

Publications (2)9.56 Total impact

• Source

  Available from: Robert Daniel Beauchamp

  Article: A network-based gene expression signature informs prognosis and treatment for colorectal cancer patients.

  Mingguang Shi, R Daniel Beauchamp, Bing Zhang
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  ABSTRACT: Several studies have reported gene expression signatures that predict recurrence risk in stage II and III colorectal cancer (CRC) patients with minimal gene membership overlap and undefined biological relevance. The goal of this study was to investigate biological themes underlying these signatures, to infer genes of potential mechanistic importance to the CRC recurrence phenotype and to test whether accurate prognostic models can be developed using mechanistically important genes. We investigated eight published CRC gene expression signatures and found no functional convergence in Gene Ontology enrichment analysis. Using a random walk-based approach, we integrated these signatures and publicly available somatic mutation data on a protein-protein interaction network and inferred 487 genes that were plausible candidate molecular underpinnings for the CRC recurrence phenotype. We named the list of 487 genes a NEM signature because it integrated information from Network, Expression, and Mutation. The signature showed significant enrichment in four biological processes closely related to cancer pathophysiology and provided good coverage of known oncogenes, tumor suppressors, and CRC-related signaling pathways. A NEM signature-based Survival Support Vector Machine prognostic model was trained using a microarray gene expression dataset and tested on an independent dataset. The model-based scores showed a 75.7% concordance with the real survival data and separated patients into two groups with significantly different relapse-free survival (p = 0.002). Similar results were obtained with reversed training and testing datasets (p = 0.007). Furthermore, adjuvant chemotherapy was significantly associated with prolonged survival of the high-risk patients (p = 0.006), but not beneficial to the low-risk patients (p = 0.491). The NEM signature not only reflects CRC biology but also informs patient prognosis and treatment response. Thus, the network-based data integration method provides a convergence between biological relevance and clinical usefulness in gene signature development.
  PLoS ONE 01/2012; 7(7):e41292. · 4.09 Impact Factor
• Article: Semi-supervised learning improves gene expression-based prediction of cancer recurrence.

  Mingguang Shi, Bing Zhang
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  ABSTRACT: Gene expression profiling has shown great potential in outcome prediction for different types of cancers. Nevertheless, small sample size remains a bottleneck in obtaining robust and accurate classifiers. Traditional supervised learning techniques can only work with labeled data. Consequently, a large number of microarray data that do not have sufficient follow-up information are disregarded. To fully leverage all of the precious data in public databases, we turned to a semi-supervised learning technique, low density separation (LDS). Using a clinically important question of predicting recurrence risk in colorectal cancer patients, we demonstrated that (i) semi-supervised classification improved prediction accuracy as compared with the state of the art supervised method SVM, (ii) performance gain increased with the number of unlabeled samples, (iii) unlabeled data from different institutes could be employed after appropriate processing and (iv) the LDS method is robust with regard to the number of input features. To test the general applicability of this semi-supervised method, we further applied LDS on human breast cancer datasets and also observed superior performance. Our results demonstrated great potential of semi-supervised learning in gene expression-based outcome prediction for cancer patients. bing.zhang@vanderbilt.edu. Supplementary data are available at Bioinformatics online.
  Bioinformatics 09/2011; 27(21):3017-23. · 5.47 Impact Factor