TMA Navigator: network inference, patient stratification and survival analysis with tissue microarray data

Abstract

Tissue microarrays (TMAs) allow multiplexed analysis of tissue samples and are frequently used to estimate biomarker protein expression in tumour biopsies. TMA Navigator (www.tmanavigator.org) is an open access web application for analysis of TMA data and related information, accommodating categorical, semi-continuous and continuous expression scores. Non-biological variation, or batch effects, can hinder data analysis and may be mitigated using the ComBat algorithm, which is incorporated with enhancements for automated application to TMA data. Unsupervised grouping of samples (patients) is provided according to Gaussian mixture modelling of marker scores, with cardinality selected by Bayesian information criterion regularization. Kaplan–Meier survival analysis is available, including comparison of groups identified by mixture modelling using the Mantel-Cox log-rank test. TMA Navigator also supports network inference approaches useful for TMA datasets, which often constitute comparatively few markers. Tissue and cell-type specific networks derived from TMA expression data offer insights into the molecular logic underlying pathophenotypes, towards more effective and personalized medicine. Output is interactive, and results may be exported for use with external programs. Private anonymous access is available, and user accounts may be generated for easier data management.

Synthetic protein interactions reveal a functional map of the cell

“…To understand whether associations to similar areas of the cell create growth defects from common sets of query proteins, we compared the SPIs generated from each target protein. Spearman’s correlation coefficient analysis ( Lubbock et al, 2013 ) indicates that, in specific cases, SPI screens using target proteins from the same cellular compartment give similar SPIs ( Figure 4B ). For example, the Pus1 and Rad52 target proteins, which are both in the nucleus, produce SPIs with a similar set of query GFP proteins.…”

Expression of glycolytic enzymes in ovarian cancers and evaluation of the glycolytic pathway as a strategy for ovarian cancer treatment

“…Expression values were averaged from either two or three replicates. Spearman non-parametric correlation and network analysis were conducted using TMA Navigator [ 42 ]. Correlation heatmaps were generated using the same software ( http://www.tmanavigator.org /).…”

Characterisation of male breast cancer: a descriptive biomarker study from a large patient series

“…A dataset containing scores for these biomarkers was uploaded to TMA Navigator29. Dendograms and correlation networks were generated providing abstraction of the relationships between multiple markers.…”