Summary: With increased generation of high-resolution sequence-based 'Omics' data, detecting statistically significant effects at different genomic locations and scales has become key to addressing several scientific questions. IWTomics is an R/Bioconductor package (integrated in Galaxy) that, exploiting sophisticated Functional Data Analysis techniques (i.e. statistical techniques that deal with the analysis of curves), allows users to pre-process, visualize and test these data at multiple locations and scales. The package provides a friendly, flexible and complete workflow that can be employed in many genomic and epigenomic applications. Availability and implementation: IWTomics is freely available at the Bioconductor website (http://bioconductor.org/packages/IWTomics) and on the main Galaxy instance (https://usegalaxy.org/). Supplementary information: Supplementary data are available at Bioinformatics online.

SUMMARY: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) generates local accumulations of sequencing reads on the genome ("peaks"), which correspond to specific protein-DNA interactions or chromatin modifications. Peaks are detected by considering their total area above a background signal, usually neglecting their shapes, which instead may convey additional biological information. We present FunChIP, an R/Bioconductor package for clustering peaks according to a functional representation of their shapes: after approximating their profiles with cubic B-splines, FunChIP minimizes their functional distance and classifies the peaks applying a k-mean alignment and clustering algorithm. The whole pipeline is user-friendly and provides visualization functions for a quick inspection of the results. An application to the transcription factor Myc in 3T9 murine fibroblasts shows that clusters of peaks with different shapes are associated with different genomic locations and different transcriptional regulatory activity. AVAILABILITY AND IMPLEMENTATION: The package is implemented in R and is available under Artistic Licence 2.0 from the Bioconductor website (http://bioconductor.org/packages/FunChIP). CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Diffusion MRI is a key in-vivo non invasive imaging capability that can probe the microstructure of the brain. However, its limited resolution requires complex voxelwise generative models of the diffusion. Diffusion Compartment (DC) models divide the voxel into smaller compartments in which diffusion is homogeneous. We present a comprehensive framework for maximum likelihood estimation (MLE) of such models that jointly features ML estimators of (i) the baseline MR signal, (ii) the noise variance, (iii) compartment proportions, and (iv) diffusion-related parameters. ML estimators are key to providing reliable mapping of brain microstructure as they are asymptotically unbiased and of minimal variance. We compare our algorithm (which efficiently exploits analytical properties of MLE) to alternative implementations and a state-of-the-art strategy. Simulation results show that our approach offers the best reduction in computational burden while guaranteeing convergence of numerical estimators to the MLE. In-vivo results also reveal remarkably reliable microstructure mapping in areas as complex as the centrum semi-ovale. Our ML framework accommodates any DC model and is available freely for multi-tensor models as part of the ANIMA software ( https://github.com/Inria-Visages/Anima-Public/wiki ).

BACKGROUND: ChIP-seq experiments are widely used to detect and study DNA-protein interactions, such as transcription factor binding and chromatin modifications. However, downstream analysis of ChIP-seq data is currently restricted to the evaluation of signal intensity and the detection of enriched regions (peaks) in the genome. Other features of peak shape are almost always neglected, despite the remarkable differences shown by ChIP-seq for different proteins, as well as by distinct regions in a single experiment. RESULTS: We hypothesize that statistically significant differences in peak shape might have a functional role and a biological meaning. Thus, we design five indices able to summarize peak shapes and we employ multivariate clustering techniques to divide peaks into groups according to both their complexity and the intensity of their coverage function. In addition, our novel analysis pipeline employs a range of statistical and bioinformatics techniques to relate the obtained peak shapes to several independent genomic datasets, including other genome-wide protein-DNA maps and gene expression experiments. To clarify the meaning of peak shape, we apply our methodology to the study of the erythroid transcription factor GATA-1 in K562 cell line and in megakaryocytes. CONCLUSIONS: Our study demonstrates that ChIP-seq profiles include information regarding the binding of other proteins beside the one used for precipitation. In particular, peak shape provides new insights into cooperative transcriptional regulation and is correlated to gene expression.

This paper addresses the issue of the classification of accident scenarios generated in a dynamic safety and reliability analyses of a Nuclear Power Plant (NPP) equipped with a Digital Instrumentation and Control system (I&C). More specifically, the classification of the final state reached by the system at the end of an accident scenario is performed by Fuzzy C-Means clustering the Functional Principal Components (FPCs) of selected relevant process variables. The approach allows capturing the characteristics of the process evolution determined by the occurrence, timing, and magnitudes of the fault events. An illustrative case study is considered, regarding the fault scenarios of the digital I&C system of the Lead Bismuth Eutectic eXperimental Accelerator Driven System (LBE-XADS). The results obtained are compared with those of the Kth Nearest Neighbor (KNN), and Classification and Regression Tree (CART) classifiers.