AMT, accurate mass and time; AUC, area under the receiver operating characteristic curve; CBS, cystathionine beta synthase; selleck chemicals FAM3C, family with sequence similarity 3, member C; GST, glutathione S-transferase; HCV, hepatitis C virus; HDAC, histone deacetylase; HLA-C, major histocompatibility class 1 antigen C; IGFBP7, insulin-like growth factor binding protein 7; IPA, Ingenuity Pathways Analysis; LC-MS, liquid chromatography/mass spectrometry; LGALS3, galectin 3; MYH11, myosin, heavy chain 11; PRKAR2A, protein kinase A RII alpha; SVD-MDS, singular value

decomposition initialized multidimensional scaling; TPM1, tropomyosin 1. This study was approved by the Institutional Review Boards for Human Subject Review at both the University of Washington and Pacific Northwest National Laboratory in accordance with federal regulations. All percutaneous core needle biopsy and serum specimens were obtained with written informed consent from HCV-infected patients who underwent liver transplantation at the

University of Washington Medical Center during 2003-2004. No donor livers were obtained from executed prisoners or other institutionalized persons. For proteome analysis, the analyzed cohort contained a total of 24 biopsy specimens obtained from 15 patients (Supporting Table 1). Statistical comparisons of clinical covariates were performed using JMP version 6.0 (SAS Institute, Cary, NC) and are reported in Table 1. An independent Student t test was used for continuous variables and a two-tailed Fisher’s exact test buy MK0683 was used for categorical variables; P ≤ 0.05 was considered statistically significant. For metabolite analysis, the analyzed cohort contained serum samples from a total Montelukast Sodium of 60 patients, including six represented in our proteome analysis (Supporting Table 2). All patients underwent transplantation due to HCV-associated cirrhosis, and all developed recurrent HCV infection. Fibrosis stage was scored by histological evaluation performed by a single pathologist using the Batts-Ludwig

scoring system.11 At the time of biopsy, all research samples were collected at the bedside, flash frozen, and stored at −80°C until use. Peptide digests were prepared as previously described3, 5 and analyzed in triplicate utilizing a high mass accuracy liquid chromatography/mass spectrometry (LC-MS) Exactive platform (Thermo Electron Corporation, San Jose, CA). Identification of the detected peptide peaks was performed using the accurate mass and time (AMT) tag approach as described.3, 5, 12 Data quality was assessed at the technical replicate level via Pearson correlation. Mass spectrometry runs exhibiting considerable deviation based on both correlation and peptide coverage in comparison to technical and biological replicates were removed from the dataset.