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


RESULTS
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.


CONCLUSIONS
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.
Division of Clinical Epidemiology, First Hospital of the Jilin University, 71Xinmin Street, Changchun, Jilin 130021, China. stian@rockefeller.edu.
Suyan
S
Tian
Howard H
HH
Chang
Chi
C
Wang
Jing
J
Jiang
Xiaomei
X
Wang
Junqi
J
Niu
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*