Introduction:
Non-Alcoholic Steatohepatitis (NASH) is an advanced stage of Non-Alcoholic Fatty Liver Disease (NAFLD) characterized by liver inflammation and damage, potentially progressing to cirrhosis or liver cancer. Accurate and non-invasive biomarkers for NASH are urgently needed for early diagnosis and monitoring. The UK Biobank, with its extensive biobank of serum samples and detailed clinical data, offers a unique resource for this purpose. This proposal aims to utilize UK Biobank data to identify and validate biomarkers for NASH using advanced proteomics techniques.
Objectives:
To identify serum biomarkers associated with NASH using proteomics analysis of UK Biobank data.
To validate these biomarkers in an independent dataset and evaluate their diagnostic performance and clinical relevance.
Study Sample
Access UK Biobank data, proteomics data and associated clinical records and social demographic data. Select samples from participants diagnosed with NASH (based on liver biopsy or imaging where available) and controls with simple steatosis or healthy liver profiles. Ensure a matched case-control study with sufficient representation of NASH cases and controls. Perform high-throughput proteomic analysis using mass spectrometry on the selected serum samples.
Data Analysis:
Apply bioinformatics tools for data processing, including normalization, differential expression analysis, and biomarker discovery. Identify proteins with significant differential expression between NASH and non-NASH groups.
Biomarker Validation:
Validate the identified biomarkers in an independent subset of UK Biobank data or additional external cohorts using quantitative assays such as ELISA or Western blot.
Assess diagnostic performance metrics such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
