Email updates

Keep up to date with the latest news and content from BMC Bioinformatics and BioMed Central.

Open Access Highly Accessed Research article

Multi-TGDR, a multi-class regularization method, identifies the metabolic profiles of hepatocellular carcinoma and cirrhosis infected with hepatitis B or hepatitis C virus

Suyan Tian1*, Howard H Chang3, Chi Wang4, Jing Jiang1, Xiaomei Wang2 and Junqi Niu2*

Author Affiliations

1 Division of Clinical Epidemiology, First Hospital of the Jilin University, 71Xinmin Street, Changchun, Jilin 130021, China

2 Department of Hepatology, First Hospital of the Jilin University, 71Xinmin Street, Changchun, Jilin 130021, China

3 Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Atlanta, GA 30322, USA

4 Department of Biostatistics and Markey Cancer Center, University of Kentucky, 800 Rose St., Lexington, KY 40536, USA

For all author emails, please log on.

BMC Bioinformatics 2014, 15:97  doi:10.1186/1471-2105-15-97

Published: 4 April 2014



Over the last decade, metabolomics has evolved into a mainstream enterprise utilized by many laboratories globally. Like other “omics” data, metabolomics data has the characteristics of a smaller sample size compared to the number of features evaluated. Thus the selection of an optimal subset of features with a supervised classifier is imperative. We extended an existing feature selection algorithm, threshold gradient descent regularization (TGDR), to handle multi-class classification of “omics” data, and proposed two such extensions referred to as multi-TGDR. Both multi-TGDR frameworks were used to analyze a metabolomics dataset that compares the metabolic profiles of hepatocellular carcinoma (HCC) infected with hepatitis B (HBV) or C virus (HCV) with that of cirrhosis induced by HBV/HCV infection; the goal was to improve early-stage diagnosis of HCC.


We applied two multi-TGDR frameworks to the HCC metabolomics data that determined TGDR thresholds either globally across classes, or locally for each class. Multi-TGDR global model selected 45 metabolites with a 0% misclassification rate (the error rate on the training data) and had a 3.82% 5-fold cross-validation (CV-5) predictive error rate. Multi-TGDR local selected 48 metabolites with a 0% misclassification rate and a 5.34% CV-5 error rate.


One important advantage of multi-TGDR local is that it allows inference for determining which feature is related specifically to the class/classes. Thus, we recommend multi-TGDR local be used because it has similar predictive performance and requires the same computing time as multi-TGDR global, but may provide class-specific inference.

Threshold gradient descent regularization (TGDR); Multi-class classification; Metabolic profile; Hepatocellular carcinoma (HCC); Feature selection; Metabolomics; Omics data