BACKGROUND: MicroRNAs, small noncoding RNAs, are conserved in many species, and they are key regulators that mediate post-transcriptional gene silencing. Since biologists cannot perform experiments for each of target genes of thousands of microRNAs in numerous specific conditions, prediction on microRNA target genes has been extensively investigated. A general framework is a two-step process of selecting target candidates based on sequence and binding energy features and then predicting targets based on negative correlation of microRNAs and their targets. However, there are few methods that are designed for target predictions using time-series gene expression data. RESULTS: In this article, we propose a new pipeline, mirTime, that predicts microRNA targets by integrating sequence features and time-series expression profiles in a specific experimental condition. The most important feature of mirTime is that it uses the Gaussian process regression model to measure data at unobserved or unpaired time points. In experiments with two datasets in different experimental conditions and cell types, condition-specific target modules reported in the original papers were successfully predicted with our pipeline. The context specificity of target modules was assessed with three (correlation-based, target gene-based and network-based) evaluation criteria. mirTime showed better performance than existing expression-based microRNA target prediction methods in all three criteria. AVAILABILITY AND IMPLEMENTATION: mirTime is available at https://github.com/mirTime/mirtime. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Identifying biologically meaningful gene expression patterns from time series gene expression data is important to understand the underlying biological mechanisms. To identify significantly perturbed gene sets between different phenotypes, analysis of time series transcriptome data requires consideration of time and sample dimensions. Thus, the analysis of such time series data seeks to search gene sets that exhibit similar or different expression patterns between two or more sample conditions, constituting the three-dimensional data, i.e. gene-time-condition. Computational complexity for analyzing such data is very high, compared to the already difficult NP-hard two dimensional biclustering algorithms. Because of this challenge, traditional time series clustering algorithms are designed to capture co-expressed genes with similar expression pattern in two sample conditions. RESULTS: We present a triclustering algorithm, TimesVector, specifically designed for clustering three-dimensional time series data to capture distinctively similar or different gene expression patterns between two or more sample conditions. TimesVector identifies clusters with distinctive expression patterns in three steps: (i) dimension reduction and clustering of time-condition concatenated vectors, (ii) post-processing clusters for detecting similar and distinct expression patterns and (iii) rescuing genes from unclassified clusters. Using four sets of time series gene expression data, generated by both microarray and high throughput sequencing platforms, we demonstrated that TimesVector successfully detected biologically meaningful clusters of high quality. TimesVector improved the clustering quality compared to existing triclustering tools and only TimesVector detected clusters with differential expression patterns across conditions successfully. AVAILABILITY AND IMPLEMENTATION: The TimesVector software is available at http://biohealth.snu.ac.kr/software/TimesVector/. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The brain network is usually constructed by estimating the connectivity matrix and thresholding it at an arbitrary level. The problem with this standard method is that we do not have any generally accepted criteria for determining a proper threshold. Thus, we propose a novel multiscale framework that models all brain networks generated over every possible threshold. Our approach is based on persistent homology and its various representations such as the Rips filtration, barcodes, and dendrograms. This new persistent homological framework enables us to quantify various persistent topological features at different scales in a coherent manner. The barcode is used to quantify and visualize the evolutionary changes of topological features such as the Betti numbers over different scales. By incorporating additional geometric information to the barcode, we obtain a single linkage dendrogram that shows the overall evolution of the network. The difference between the two networks is then measured by the Gromov-Hausdorff distance over the dendrograms. As an illustration, we modeled and differentiated the FDG-PET based functional brain networks of 24 attention-deficit hyperactivity disorder children, 26 autism spectrum disorder children, and 11 pediatric control subjects.

Partial correlation is a useful connectivity measure for brain networks, especially, when it is needed to remove the confounding effects in highly correlated networks. Since it is difficult to estimate the exact partial correlation under the small- n large- p situation, a sparseness constraint is generally introduced. In this paper, we consider the sparse linear regression model with a l(1)-norm penalty, also known as the least absolute shrinkage and selection operator (LASSO), for estimating sparse brain connectivity. LASSO is a well-known decoding algorithm in the compressed sensing (CS). The CS theory states that LASSO can reconstruct the exact sparse signal even from a small set of noisy measurements. We briefly show that the penalized linear regression for partial correlation estimation is related to CS. It opens a new possibility that the proposed framework can be used for a sparse brain network recovery. As an illustration, we construct sparse brain networks of 97 regions of interest (ROIs) obtained from FDG-PET imaging data for the autism spectrum disorder (ASD) children and the pediatric control (PedCon) subjects. As validation, we check the network reproducibilities by leave-one-out cross validation and compare the clustered structures derived from the brain networks of ASD and PedCon.