MOTIVATION: Genotype imputation has the potential to increase the amount of information that can be gained from the often limited biological material available in ancient samples. As many widely used tools have been developed with modern data in mind, their design is not necessarily reflective of the requirements in studies of ancient DNA. Here, we investigate if an imputation method based on the full probabilistic Li and Stephens model of haplotype frequencies might be beneficial for the particular challenges posed by ancient data. RESULTS: We present an implementation called prophaser and compare imputation performance to two alternative pipelines that have been used in the ancient DNA community based on the Beagle software. Considering empirical ancient data downsampled to lower coverages as well as present-day samples with artificially thinned genotypes, we show that the proposed method is advantageous at lower coverages, where it yields improved accuracy and ability to capture rare variation. The software prophaser is optimized for running in a massively parallel manner and achieved reasonable runtimes on the experiments performed when executed on a GPU. AVAILABILITY AND IMPLEMENTATION: The C++ code for prophaser is available in the GitHub repository https://github.com/scicompuu/prophaser. SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online.

BACKGROUND: Despite continuing technological advances, the cost for large-scale genotyping of a high number of samples can be prohibitive. The purpose of this study is to design a cost-saving strategy for SNP genotyping. We suggest making use of pooling, a group testing technique, to drop the amount of SNP arrays needed. We believe that this will be of the greatest importance for non-model organisms with more limited resources in terms of cost-efficient large-scale chips and high-quality reference genomes, such as application in wildlife monitoring, plant and animal breeding, but it is in essence species-agnostic. The proposed approach consists in grouping and mixing individual DNA samples into pools before testing these pools on bead-chips, such that the number of pools is less than the number of individual samples. We present a statistical estimation algorithm, based on the pooling outcomes, for inferring marker-wise the most likely genotype of every sample in each pool. Finally, we input these estimated genotypes into existing imputation algorithms. We compare the imputation performance from pooled data with the Beagle algorithm, and a local likelihood-aware phasing algorithm closely modeled on MaCH that we implemented. RESULTS: We conduct simulations based on human data from the 1000 Genomes Project, to aid comparison with other imputation studies. Based on the simulated data, we find that pooling impacts the genotype frequencies of the directly identifiable markers, without imputation. We also demonstrate how a combinatorial estimation of the genotype probabilities from the pooling design can improve the prediction performance of imputation models. Our algorithm achieves 93% concordance in predicting unassayed markers from pooled data, thus it outperforms the Beagle imputation model which reaches 80% concordance. We observe that the pooling design gives higher concordance for the rare variants than traditional low-density to high-density imputation commonly used for cost-effective genotyping of large cohorts. CONCLUSIONS: We present promising results for combining a pooling scheme for SNP genotyping with computational genotype imputation on human data. These results could find potential applications in any context where the genotyping costs form a limiting factor on the study size, such as in marker-assisted selection in plant breeding.

Recent work in word spotting in handwritten documents has yielded impressive results, largely using supervised learning systems, which are dependent on manually annotated data, making deployment to new collections a significant effort. In this paper, we propose an approach that utilises transcripts without bounding box annotations to train segmentation-free query-by-string word spotting models, given a partially trained model. This is done through a training-free alignment procedure based on hidden Markov models. This procedure creates a tentative mapping between word region proposals and the transcriptions to automatically create additional weakly annotated training data, without choosing any single alignment possibility as the correct one. When only using between 1% and 10% of the fully annotated training sets for partial convergence, we automatically annotate the remaining training data and achieve successful training using it. In terms of mean average precision, our final trained model then comes within a few percent of the performance of a model trained with the full training set on all our datasets. We believe that this will be a significant advance towards a more general use of word spotting, since digital transcription data will already exist for parts of many collections of interest.

BACKGROUND: The advent of next-generation sequencing (NGS) has made whole-genome sequencing of cohorts of individuals a reality. Primary datasets of raw or aligned reads of this sort can get very large. For scientific questions where curated called variants are not sufficient, the sheer size of the datasets makes analysis prohibitively expensive. In order to make re-analysis of such data feasible without the need to have access to a large-scale computing facility, we have developed a highly scalable, storage-agnostic framework, an associated API and an easy-to-use web user interface to execute custom filters on large genomic datasets. RESULTS: We present BAMSI, a Software as-a Service (SaaS) solution for filtering of the 1000 Genomes phase 3 set of aligned reads, with the possibility of extension and customization to other sets of files. Unique to our solution is the capability of simultaneously utilizing many different mirrors of the data to increase the speed of the analysis. In particular, if the data is available in private or public clouds - an increasingly common scenario for both academic and commercial cloud providers - our framework allows for seamless deployment of filtering workers close to data. We show results indicating that such a setup improves the horizontal scalability of the system, and present a possible use case of the framework by performing an analysis of structural variation in the 1000 Genomes data set. CONCLUSIONS: BAMSI constitutes a framework for efficient filtering of large genomic data sets that is flexible in the use of compute as well as storage resources. The data resulting from the filter is assumed to be greatly reduced in size, and can easily be downloaded or routed into e.g. a Hadoop cluster for subsequent interactive analysis using Hive, Spark or similar tools. In this respect, our framework also suggests a general model for making very large datasets of high scientific value more accessible by offering the possibility for organizations to share the cost of hosting data on hot storage, without compromising the scalability of downstream analysis.

In quantitative trait locus (QTL) mapping significance of putative QTL is often determined using permutation testing. The computational needs to calculate the significance level are immense, 104up to 108or even more permutations can be needed. We have previously introduced the PruneDIRECT algorithm for multiple QTL scan with epistatic interactions. This algorithm has specific strengths for permutation testing. Here, we present a flexible, parallel computing framework for identifying multiple interacting QTL using the PruneDIRECT algorithm which uses the map-reduce model as implemented in Hadoop. The framework is implemented in R, a widely used software tool among geneticists. This enables users to rearrange algorithmic steps to adapt genetic models, search algorithms, and parallelization steps to their needs in a flexible way. Our work underlines the maturity of accessing distributed parallel computing for computationally demanding bioinformatics applications through building workflows within existing scientific environments. We investigate the PruneDIRECT algorithm, comparing its performance to exhaustive search and DIRECT algorithm using our framework on a public cloud resource. We find that PruneDIRECT is vastly superiorfor permutation testing, and perform 2 × 105permutations for a 2D QTL problem in 15 hours, using 100 cloud processes. We show that our framework scales out almost linearly for a 3D QTL search.