IsoGeneGUI: Multiple Approaches for Dose-Response Analysis of Microarray Data Using R

The analysis of transcriptomic experiments with ordered covariates, such as dose-response data, has become a central topic in bioinformatics, in particular in omics studies. Consequently, multiple R packages on CRAN and Bioconductor are designed to analyse microarray data from various perspectives under the assumption of order restriction. We introduce the new R package IsoGene Graphical User Interface (IsoGeneGUI), an extension of the original IsoGene package that includes methods from most of available R packages designed for the analysis of order restricted microarray data, namely orQA, ORIClust, goric and ORCME. The methods included in the new IsoGeneGUI range from inference and estimation to model selection and clustering tools. The IsoGeneGUI is not only the most complete tool for the analysis of order restricted microarray experiments available in R but also it can be used to analyse other types of dose-response data. The package provides all the methods in a user friendly fashion, so analyses can be implemented by users with limited knowledge of R programming

Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity

<div><p>Background and aims</p><p>Antithrombin III (ATIII) has been reported to be associated with liver pathologies and was shown to predict outcome in patients undergoing liver resection for hepatocellular carcinoma. We now aimed to assess whether perioperative ATIII-activity could predict postoperative outcome in patients without underlying liver disease, as well as in a routine clinical setting of patients undergoing hepatic resection.</p><p>Methods</p><p>ATIII-activity was evaluated preoperatively and on the first (POD1) and fifth day after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC). We further aimed to prospectively validate our results in a set of 177 consecutive patients undergoing hepatic resection.</p><p>Results</p><p>Patients developing postoperative liver dysfunction (LD) had a more pronounced postoperative decrease in ATIII-activity (P<0.001). ATIII-activity on POD1 significantly predicted postoperative LD (P<0.001, AUC = 84.4%) and remained independent upon multivariable analysis. A cut-off value of 61.5% ATIII-activity was determined using ROC analysis. This cut-off was vital to identify high-risk patients for postoperative LD, morbidity, severe morbidity and mortality (P<0.001, respectively) with a highly accurate negative predictive value of 97%, which could be confirmed for LD (P<0.001) and mortality (P = 0.014) in our independent validation cohort. Further, mCRC patients below our cut-off suffered from a significantly decreased overall survival (OS) at 1 and 3 years after surgery (P = 0.011, P = 0.025).</p><p>Conclusions</p><p>The routine laboratory parameter ATIII-activity on POD1 independently predicted postoperative LD and was associated with clinical outcome. Patients with a postoperative ATIII-activity <61.5% might benefit from close monitoring and timely initiation of supportive therapy.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01700231" target="_blank">NCT01700231</a></p></div

Decision tree for postoperative risk stratification.

<p>Combination of ATIII-activity and SB values on POD1 allows highly specific discrimination of patients risk for postoperative LD.</p

ATIII-activity on POD1 competes other markers in the prediction of postoperative LD.

<p>Predictive value of ATIII-activity, CRP, fibrinogen, SB, PT, AST, ALT and GGT on POD1 to predict postoperative LD using receiver operating characteristics (ROC) analysis was compared.</p