TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data.

The Cancer Genome Atlas (TCGA) research network has made public a large collection of clinical and molecular phenotypes of more than 10 000 tumor patients across 33 different tumor types. Using this cohort, TCGA has published over 20 marker papers detailing the genomic and epigenomic alterations associated with these tumor types. Although many important discoveries have been made by TCGA's research network, opportunities still exist to implement novel methods, thereby elucidating new biological pathways and diagnostic markers. However, mining the TCGA data presents several bioinformatics challenges, such as data retrieval and integration with clinical data and other molecular data types (e.g. RNA and DNA methylation). We developed an R/Bioconductor package called TCGAbiolinks to address these challenges and offer bioinformatics solutions by using a guided workflow to allow users to query, download and perform integrative analyses of TCGA data. We combined methods from computer science and statistics into the pipeline and incorporated methodologies developed in previous TCGA marker studies and in our own group. Using four different TCGA tumor types (Kidney, Brain, Breast and Colon) as examples, we provide case studies to illustrate examples of reproducibility, integrative analysis and utilization of different Bioconductor packages to advance and accelerate novel discoveries.

Unsupervised identification of states from voltage recordings of neural networks.

BACKGROUND: Modern techniques for multi-neuronal recording produce large amounts of data. There is no automatic procedure for the identification of states in recurrent voltage patterns. NEW METHOD: We propose NetSAP (Network States And Pathways), a data-driven analysis method that is able to recognize multi-neuron voltage patterns (states). To capture the subtle differences between snapshots in voltage recordings, NetSAP infers the underlying functional neural network in a time-resolved manner with a sliding window approach. Then NetSAP identifies states from a reordering of the time series of inferred networks according to a user-defined metric. The procedure for unsupervised identification of states was developed originally for the analysis of molecular dynamics simulations of proteins. RESULTS: We tested NetSAP on neural network simulations of GABAergic inhibitory interneurons. Most simulation parameters are chosen to reproduce literature observations, and we keep noise terms as control parameters to regulate the coherence of the simulated signals. NetSAP is able to identify multiple states even in the case of high internal noise and low signal coherence. We provide evidence that NetSAP is robust for networks with up to about 50% of the neurons spiking randomly. NetSAP is scalable and its code is open source. COMPARISON WITH EXISTING METHODS: NetSAP outperforms common analysis techniques, such as PCA and k-means clustering, on a simulated recording of voltage traces of 50 neurons. CONCLUSIONS: NetSAP analysis is an efficient tool to identify voltage patterns from neuronal recordings.