A New Strategy for Analyzing Time-Series Data Using Dynamic Networks: Identifying Prospective Biomarkers of Hepatocellular Carcinoma

Sci Rep. 2016 Aug 31:6:32448. doi: 10.1038/srep32448.

Abstract

Time-series metabolomics studies can provide insight into the dynamics of disease development and facilitate the discovery of prospective biomarkers. To improve the performance of early risk identification, a new strategy for analyzing time-series data based on dynamic networks (ATSD-DN) in a systematic time dimension is proposed. In ATSD-DN, the non-overlapping ratio was applied to measure the changes in feature ratios during the process of disease development and to construct dynamic networks. Dynamic concentration analysis and network topological structure analysis were performed to extract early warning information. This strategy was applied to the study of time-series lipidomics data from a stepwise hepatocarcinogenesis rat model. A ratio of lyso-phosphatidylcholine (LPC) 18:1/free fatty acid (FFA) 20:5 was identified as the potential biomarker for hepatocellular carcinoma (HCC). It can be used to classify HCC and non-HCC rats, and the area under the curve values in the discovery and external validation sets were 0.980 and 0.972, respectively. This strategy was also compared with a weighted relative difference accumulation algorithm (wRDA), multivariate empirical Bayes statistics (MEBA) and support vector machine-recursive feature elimination (SVM-RFE). The better performance of ATSD-DN suggests its potential for a more complete presentation of time-series changes and effective extraction of early warning information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Area Under Curve
  • Bayes Theorem
  • Benchmarking
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / pathology
  • Disease Models, Animal
  • Disease Progression
  • Early Diagnosis
  • Fatty Acids, Nonesterified / blood*
  • Hepatitis / blood
  • Hepatitis / complications
  • Hepatitis / diagnosis*
  • Hepatitis / pathology
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / etiology
  • Liver Neoplasms / pathology
  • Lysophosphatidylcholines / blood*
  • Male
  • Metabolomics / methods
  • Rats
  • Rats, Sprague-Dawley
  • Support Vector Machine
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Fatty Acids, Nonesterified
  • Lysophosphatidylcholines