MOTIVATION: 1H-NMR metabolomics is rapidly becoming a standard resource in large epidemiological studies to acquire metabolic profiles in large numbers of samples in a relatively low-priced and standardized manner. Concomitantly, metabolomics-based models are increasingly developed that capture disease risk or clinical risk factors. These developments raise the need for user-friendly toolbox to inspect new 1H-NMR metabolomics data and project a wide array of previously established risk models. RESULTS: We present MiMIR (Metabolomics-based Models for Imputing Risk), a graphical user interface that provides an intuitive framework for ad hoc statistical analysis of Nightingale Health's 1H-NMR metabolomics data and allows for the projection and calibration of 24 pre-trained metabolomics-based models, without any pre-required programming knowledge. AVAILABILITY AND IMPLEMENTATION: The R-shiny package is available in CRAN or downloadable at https://github.com/DanieleBizzarri/MiMIR, together with an extensive user manual (also available as Supplementary Documents to the article). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Abstract Through the quantification of physical activity energy expenditure (PAEE), health care monitoring has the potential to stimulate vital and healthy ageing, inducing behavioural changes in older people and linking these to personal health gains. To be able to measure PAEE in a health care perspective, methods from wearable accelerometers have been developed, however, mainly targeted towards younger people. Since elderly subjects differ in energy requirements and range of physical activities, the current models may not be suitable for estimating PAEE among the elderly. Furthermore, currently available methods seem to be either simple but non-generalizable or require elaborate (manual) feature construction steps. Because past activities influence present PAEE, we propose a modeling approach known for its ability to model sequential data, the recurrent neural network (RNN). To train the RNN for an elderly population, we used the growing old together validation (GOTOV) dataset with 34 healthy participants of 60 years and older (mean 65 years old), performing 16 different activities. We used accelerometers placed on wrist and ankle, and measurements of energy counts by means of indirect calorimetry. After optimization, we propose an architecture consisting of an RNN with 3 GRU layers and a feedforward network combining both accelerometer and participant-level data. Our efforts included switching mean to standard deviation for down-sampling the input data and combining temporal and static data (person-specific details such as age, weight, BMI). The resulting architecture produces accurate PAEE estimations while decreasing training input and time by a factor of 10. Subsequently, compared to the state-of-the-art, it is capable to integrate longer activity data which lead to more accurate estimations of low intensity activities EE. It can thus be employed to investigate associations of PAEE with vitality parameters of older people related to metabolic and cognitive health and mental well-being.

Abstract A population group that is often overlooked in the recent revolution of self-tracking is the group of older people. This growing proportion of the general population is often faced with increasing health issues and discomfort. In order to come up with lifestyle advice towards the elderly, we need the ability to quantify their lifestyle, before and after an intervention. This research focuses on the task of activity recognition (AR) from accelerometer data. With that aim, we collect a substantial labelled dataset of older individuals wearing multiple devices simultaneously and performing a strict protocol of 16 activities (the GOTOV dataset, $$N=28$$ N=28 ). Using this dataset, we trained Random Forest AR models, under varying sensor set-ups and levels of activity description granularity. The model that combines ankle and wrist accelerometers (GENEActiv) produced the best results (accuracy $$>80\%$$ >80% ) for 16-class classification. At the same time, when additional physiological information is used, the accuracy increased ( $$>85\%$$ >85% ). To further investigate the role of granularity in our predictions, we developed the LARA algorithm, which uses a hierarchical ontology that captures prior biological knowledge to increase or decrease the level of activity granularity (merge classes). As a result, a 12-class model in which the different paces of walking were merged showed a performance above $$93\%$$ 93% . Testing this 12-class model in labelled free-living pilot data, the mean balanced accuracy appeared to be reasonably high, while using the LARA algorithm, we show that a 7-class model (lying down, sitting, standing, household, walking, cycling, jumping) was optimal for accuracy and granularity. Finally, we demonstrate the use of the latter model in unlabelled free-living data from a larger lifestyle intervention study. In this paper, we make the validation data as well as the derived prediction models available to the community.

MOTIVATION: Dispersed duplications (DDs) such as transposon element insertions and copy number variations are ubiquitous in the human genome. They have attracted the interest of biologists as well as medical researchers due to their role in both evolution and disease. The efforts of discovering DDs in high-throughput sequencing data are currently dominated by database-oriented approaches that require pre-existing knowledge of the DD elements to be detected. RESULTS: We present DD_DETECTION, a database-free approach to finding DD events in high-throughput sequencing data. DD_DETECTION is able to detect DDs purely from paired-end read alignments. We show in a comparative study that this method is able to compete with database-oriented approaches in recovering validated transposon insertion events. We also experimentally validate the predictions of DD_DETECTION on a human DNA sample, showing that it can find not only duplicated elements present in common databases but also DDs of novel type. AVAILABILITY AND IMPLEMENTATION: The software presented in this article is open source and available from https://bitbucket.org/mkroon/dd_detection.

INTRODUCTION: An increasing number of studies investigates the influence of local genetic variation on DNA methylation levels, so-called in cis methylation quantitative trait loci (meQTLs). A common multiple testing approach in genome-wide cis meQTL studies limits the false discovery rate (FDR) among all CpG-SNP pairs to 0.05 and reports on CpGs from the significant CpG-SNP pairs. However, a statistical test for each CpG is not performed, potentially increasing the proportion of CpGs falsely reported on. Here, we presented an alternative approach that properly control for multiple testing at the CpG level. RESULTS: We performed cis meQTL mapping for varying window sizes using publicly available single-nucleotide polymorphism (SNP) and 450 kb data, extracting the CpGs from the significant CpG-SNP pairs ([Formula: see text]). Using a new bait-and-switch simulation approach, we show that up to 50% of the CpGs found in the simulated data may be false-positive results. We present an alternative two-step multiple testing approach using the Simes and Benjamini-Hochberg procedures that does control the FDR among the CpGs, as confirmed by the bait-and-switch simulation. This approach indicates the use of window sizes in cis meQTL mapping studies that are significantly smaller than commonly adopted. DISCUSSION: Our approach to cis meQTL mapping properly controls the FDR at the CpG level, is computationally fast and can also be applied to cis eQTL studies. AVAILABILITY AND IMPLEMENTATION: An examplary R script for performing the Simes procedure is available as supplementary material. CONTACT: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

UNLABELLED: The Illumina 450k array is a frequently used platform for large-scale genome-wide DNA methylation studies, i.e. epigenome-wide association studies. Currently, quality control of 450k data can be performed with Illumina's GenomeStudio and is part of a limited number 450k analysis pipelines. However, GenomeStudio cannot handle large-scale studies, and existing pipelines provide limited options for quality control and neither support interactive exploration by the user. To aid the detection of bad-quality samples in large-scale genome-wide DNA methylation studies as flexible and transparent as possible, we have developed MethylAid; a visual and interactive Web application using RStudio's shiny package. Bad-quality samples are detected using sample-dependent and sample-independent quality control probes present on the array and user-adjustable thresholds. In-depth exploration of bad-quality samples can be performed using several interactive diagnostic plots. Furthermore, plots can be annotated with user-provided metadata, for example, to identify outlying batches. Our new tool makes quality assessment of 450k array data interactive, flexible and efficient and is, therefore, expected to be useful for both data analysts and core facilities. AVAILABILITY AND IMPLEMENTATION: MethylAid is implemented as an R/Bioconductor package (www.bioconductor.org/packages/3.0/bioc/html/MethylAid.html). A demo application is available from shiny.bioexp.nl/MethylAid.

MOTIVATION: RNA-seq is a powerful technology for the study of transcriptome profiles that uses deep-sequencing technologies. Moreover, it may be used for cellular phenotyping and help establishing the etiology of diseases characterized by abnormal splicing patterns. In RNA-Seq, the exact nature of splicing events is buried in the reads that span exon-exon boundaries. The accurate and efficient mapping of these reads to the reference genome is a major challenge. RESULTS: We developed PASSion, a pattern growth algorithm-based pipeline for splice site detection in paired-end RNA-Seq reads. Comparing the performance of PASSion to three existing RNA-Seq analysis pipelines, TopHat, MapSplice and HMMSplicer, revealed that PASSion is competitive with these packages. Moreover, the performance of PASSion is not affected by read length and coverage. It performs better than the other three approaches when detecting junctions in highly abundant transcripts. PASSion has the ability to detect junctions that do not have known splicing motifs, which cannot be found by the other tools. Of the two public RNA-Seq datasets, PASSion predicted ≈ 137,000 and 173,000 splicing events, of which on average 82 are known junctions annotated in the Ensembl transcript database and 18% are novel. In addition, our package can discover differential and shared splicing patterns among multiple samples. AVAILABILITY: The code and utilities can be freely downloaded from https://trac.nbic.nl/passion and ftp://ftp.sanger.ac.uk/pub/zn1/passion.