PyPedia: using the wiki paradigm as crowd sourcing environment for bioinformatics protocols

Background

Today researchers can choose from many bioinformatics protocols for all types of life sciences research, computational environments and coding languages. Although the majority of these are open source, few of them possess all virtues to maximize reuse and promote reproducible science. Wikipedia has proven a great tool to disseminate information and enhance collaboration between users with varying expertise and background to author qualitative content via crowdsourcing. However, it remains an open question whether the wiki paradigm can be applied to bioinformatics protocols.

Results

We piloted PyPedia, a wiki where each article is both implementation and documentation of a bioinformatics computational protocol in the python language. Hyperlinks within the wiki can be used to compose complex workflows and induce reuse. A RESTful API enables code execution outside the wiki. Initial content of PyPedia contains articles for population statistics, bioinformatics format conversions and genotype imputation. Use of the easy to learn wiki syntax effectively lowers the barriers to bring expert programmers and less computer savvy researchers on the same page.

Conclusions

PyPedia demonstrates how wiki can provide a collaborative development, sharing and even execution environment for biologists and bioinformaticians that complement existing resources, useful for local and multi-center research teams.

Availability

PyPedia is available online at: http://www.pypedia.com. The source code and installation instructions are available at: https://github.com/kantale/PyPedia_server. The PyPedia python library is available at: https://github.com/kantale/pypedia. PyPedia is open-source, available under the BSD 2-Clause License.

     

MM2S: personalized diagnosis of medulloblastoma patients and model systems

Background

Medulloblastoma (MB) is a highly malignant and heterogeneous brain tumour that is the most common cause of cancer-related deaths in children. Increasing availability of genomic data over the last decade had resulted in improvement of human subtype classification methods, and the parallel development of MB mouse models towards identification of subtype-specific disease origins and signaling pathways. Despite these advances, MB classification schemes remained inadequate for personalized prediction of MB subtypes for individual patient samples and across model systems. To address this issue, we developed the Medullo-Model to Subtypes ( MM2S ) classifier, a new method enabling classification of individual gene expression profiles from MB samples (patient samples, mouse models, and cell lines) against well-established molecular subtypes [Genomics 106:96-106, 2015]. We demonstrated the accuracy and flexibility of MM2S in the largest meta-analysis of human patients and mouse models to date. Here, we present a new functional package that provides an easy-to-use and fully documented implementation of the MM2S method, with additional functionalities that allow users to obtain graphical and tabular summaries of MB subtype predictions for single samples and across sample replicates. The flexibility of the MM2S package promotes incorporation of MB predictions into large Medulloblastoma-driven analysis pipelines, making this tool suitable for use by researchers.

Results

The MM2S package is applied in two case studies involving human primary patient samples, as well as sample replicates of the GTML mouse model. We highlight functions that are of use for species-specific MB classification, across individual samples and sample replicates. We emphasize on the range of functions that can be used to derive both singular and meta-centric views of MB predictions, across samples and across MB subtypes.

Conclusions

Our MM2S package can be used to generate predictions without having to rely on an external web server or additional sources. Our open-source package facilitates and extends the MM2S algorithm in diverse computational and bioinformatics contexts. The package is available on CRAN, at the following URL: https://cran.r-project.org/web/packages/MM2S/, as well as on Github at the following URLs: https://github.com/DGendoo and https://github.com/bhklab.

     

lociNGS: A Lightweight Alternative for Assessing Suitability of Next-Generation Loci for Evolutionary Analysis

Genomic enrichment methods and next-generation sequencing produce uneven coverage for the portions of the genome (the loci) they target; this information is essential for ascertaining the suitability of each locus for further analysis. lociNGS is a user-friendly accessory program that takes multi-FASTA formatted loci, next-generation sequence alignments and demographic data as input and collates, displays and outputs information about the data. Summary information includes the parameters coverage per locus, coverage per individual and number of polymorphic sites, among others. The program can output the raw sequences used to call loci from next-generation sequencing data. lociNGS also reformats subsets of loci in three commonly used formats for multi-locus phylogeographic and population genetics analyses – NEXUS, IMa2 and Migrate. lociNGS is available at https://github.com/SHird/lociNGS and is dependent on installation of MongoDB (freely available at http://www.mongodb.org/downloads). lociNGS is written in Python and is supported on MacOSX and Unix; it is distributed under a GNU General Public License.     

Speed and accuracy improvement of higher-order epistasis detection on CUDA-enabled GPUs

The discovery of higher-order epistatic interactions is an important task in the field of genome wide association studies which allows for the identification of complex interaction patterns between multiple genetic markers. Some existing bruteforce approaches explore the whole space of k-interactions in an exhaustive manner resulting in almost intractable execution times. Computational cost can be reduced drastically by restricting the search space with suitable preprocessing filters which prune unpromising candidates. Other approaches mitigate the execution time by employing massively parallel accelerators in order to benefit from the vast computational resources of these architectures. In this paper, we combine a novel preprocessing filter, namely SingleMI, with massively parallel computation on modern GPUs to further accelerate epistasis discovery. Our implementation improves both the runtime and accuracy when compared to a previous GPU counterpart that employs mutual information clustering for prefiltering. SingleMI is open source software and publicly available at: https://github.com/sleeepyjack/singlemi/.     

The scent of your enemy is my friend? The acquisition of large carnivore scent by a smaller carnivore

Scent marking is critical to intraspecific communication in many mammal species, but little is known regarding its role in communication among different species. We used 4 years of motion-triggered video to document the use of scent marking areas—termed “community scrapes”—by pumas (Puma concolor) (http://www.momo-p.com/showdetail-e.php?movieid=momo160812pc01a) and other carnivore species. We found that gray foxes (Urocyon cinereoargenteus) routinely rubbed their cheeks on puma scrapes (http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc01a), and tested a series of hypotheses to determine its function. We found that gray foxes selected puma scrapes over other objects, and cheek rubbing by foxes was also correlated with how recently a puma had visited the scrape, suggesting that foxes were intent upon accumulating fresh puma scent. Cheek rubbing by foxes was not correlated with their breeding season or with how recently another fox had visited the site. Finally we found a cascading pattern in the occurrence of pumas, coyotes (Canis latrans) and gray foxes at community scrapes, suggesting that gray foxes may use puma scent to deter predation. This is the first published study to find evidence of a subordinate species using the scent of a dominant species to communicate with heterospecifics. The behavioral cascade we found in scent marking patterns also suggests that scent marking could be a mechanism that impacts the distribution and abundance of species. Additional videos pertaining to this article include http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc02a, and http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc03a.     

<Emphasis Type="Italic">snpReady</Emphasis>: a tool to assist breeders in genomic analysis

The snpReady R package is a new instrument developed to help breeders in genomic projects such as genomic prediction and association studies. This package offers three different methods to build the genomic relationship matrix, a new imputation method for missing markers based on Wright’s theory, and a population genetic overview. Therefore, we implemented three functions (raw.data, G.matrix, and popgen). Hence, this tool allows the raw data to be transformed from different genotyping platforms to numeric matrices and performs quality control (missing data and allele frequency). Moreover, the package generates and exports four different relationship matrices (proposed by Yang et al. (N 569:565–569, 2010), VanRaden (JDS 91:4414–23, 2008), and the Gaussian kernel) depending on the purpose and software to be used in further analysis. Finally, based on the genotypic matrix, the package estimates the genetic variability, effective population size, and endogamy, among other population genetic parameters. Empirical comparisons between the method of imputation proposed and other well-known approaches have shown a lower accuracy of imputation, however, with no significant impact on the genome prediction accuracies when a lower amount of missing data is allowed. The functions and arguments were designed to carry out the preparation of genomic datasets in a straightforward, fast, and more computationally efficient way.The package and its details are available at CRAN or http://www.github.com/italo-granato/snpReady.     

Interspecific responses of wild African carnivores to odour of 3-mercapto-3-methylbutanol,a component of wildcat and leopard urine

The scent of 3-mercapto-3-methylbutanol (3-M-3-MB), a volatile component of leopard (Panthera pardus) and domestic cat (Felis silvestris catus) urine, released at about 10 ng/s from slow-release dispensers, elicited scent-marking from African civet (Civettictis civetta), small-spotted genet (Genetta genetta) and slender mongoose (Galerella sanguinea), as well as African wildcat (F. s. cafra). A female leopard was apparently repelled by the scent. The scent-marking and scent-rubbing by species other than African wildcats and leopards were unexpected and have important implications for the design of studies to investigate chemical communication between wild mammals and the use of camera traps to estimate animal numbers. Videos showing the behaviours referred to in this article are available at; http://www.momo-p.com/showdetail-e.php?movieid=momo161223fs01a; http://www.momo-p.com/showdetail-e.php?movieid=momo161223gs01a; http://www.momo-p.com/showdetail-e.php?movieid=momo161223gg01a.     

Reliability of signal transmission in stochastic nerve axon equations

We introduce a method for computing probabilities for spontaneous activity and propagation failure of the action potential in spatially extended, conductance-based neuronal models subject to noise, based on statistical properties of the membrane potential. We compare different estimators with respect to the quality of detection, computational costs and robustness and propose the integral of the membrane potential along the axon as an appropriate estimator to detect both spontaneous activity and propagation failure. Performing a model reduction we achieve a simplified analytical expression based on the linearization at the resting potential (resp. the traveling action potential). This allows to approximate the probabilities for spontaneous activity and propagation failure in terms of (classical) hitting probabilities of one-dimensional linear stochastic differential equations. The quality of the approximation with respect to the noise amplitude is discussed and illustrated with numerical results for the spatially extended Hodgkin-Huxley equations. Python simulation code is supplied on GitHub under the link https://github.com/deristnochda/Hodgkin-Huxley-SPDE.     

Paternal care behaviors of Japanese giant salamander <Emphasis Type="Italic">Andrias japonicus</Emphasis> in natural populations

Parental care among salamanders is typically provided by females. A rare case of parental care by male salamanders appears to occur in Cryptobranchidae. Yet, paternal behaviors have rarely been reported from natural populations of any Cryptobranchid salamanders, and their adaptive significance is poorly understood. The present study aimed to examine paternal care behaviors in a fully aquatic Japanese giant salamander (Andrias japonicus) in situ. At the beginning of the summer breeding season, large males, called den-masters, occupy burrows along stream banks for breeding and nesting. We videotaped post-breeding behaviors of two den-masters that stayed with the eggs, one in a natural and the other in an artificial nest in natural streams. We identified three behaviors, tail fanning, agitating and egg eating, to be parental care. Tail fanning provides oxygenated water for the eggs. We found that the den-master in the artificial nest, where dissolved oxygen level was lower, displayed tail fanning more frequently. Agitating the eggs with its head and body likely prevents yolk adhesions. The den-masters selectively ate whiter eggs that appeared to be dead or infected with water mold. This behavior, which we termed hygienic filial cannibalism, likely prevents water mold from spreading over healthy eggs. Digital video images relating to this article are available at http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj01a, http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj02a, http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj03a and http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj04a.     

PureCLIP: capturing target-specific protein–RNA interaction footprints from single-nucleotide CLIP-seq data

The iCLIP and eCLIP techniques facilitate the detection of protein–RNA interaction sites at high resolution, based on diagnostic events at crosslink sites. However, previous methods do not explicitly model the specifics of iCLIP and eCLIP truncation patterns and possible biases. We developed PureCLIP (https://github.com/skrakau/PureCLIP), a hidden Markov model based approach, which simultaneously performs peak-calling and individual crosslink site detection. It explicitly incorporates a non-specific background signal and, for the first time, non-specific sequence biases. On both simulated and real data, PureCLIP is more accurate in calling crosslink sites than other state-of-the-art methods and has a higher agreement across replicates.     

miRTrace reveals the organismal origins of microRNA sequencing data

We present here miRTrace, the first algorithm to trace microRNA sequencing data back to their taxonomic origins. This is a challenge with profound implications for forensics, parasitology, food control, and research settings where cross-contamination can compromise results. miRTrace accurately (>?99%) assigns real and simulated data to 14 important animal and plant groups, sensitively detects parasitic infection in mammals, and discovers the primate origin of single cells. Applying our algorithm to over 700 public datasets, we find evidence that over 7% are cross-contaminated and present a novel solution to clean these computationally, even after sequencing has occurred. miRTrace is freely available at https://github.com/friedlanderlab/mirtrace.     

Mating and aggressive behaviour of <Emphasis Type="Italic">Brachyrhaphis olomina</Emphasis> (Cyprinodontiformes: Poeciliidae)

Despite the increasing interest in the use of intromittent male genitalia and coercive mating behaviour in poeciliids, detailed studies of the mating behaviour of most species in this family are lacking. We describe here the mating and aggressive behaviours of Brachyrhaphis olomina, and correlate them with the condition of the female’s ovum and embryos (immature, mature and pregnant). B. olomina performed a wide range of aggressive (sidle spread, tail beating, coordinate) and mating behaviours (approximation, touch, lateral display, touch-lateral display). Some behaviours (e.g. tail beating) are shared with other poeciliids, but two sexual behaviours (touch and lateral display) and one aggressive (coordinate) behaviour may be unique to B. olomina and were not reported in a previous study. Differences in male behaviour when paired with a female with mature ovum (more mating displays, no agonistic movements) suggest that males detect the female’s reproductive condition from some distance. The distinctive nature of mating behaviour in B. olomina highlights the importance of studying different species to have a better understanding of the evolution of mating and aggressive behaviours in poeciliids. Digital video images related to the article are available at http://www.momo-p.com/showdetail-e.php?movieid=momo170720bo01a, http://www.momo-p.com/showdetail-e.php?movieid=momo170720bo02a and http://www.momo-p.com/showdetail-e.php?movieid=momo170720bo03a.     

rDolphin: a GUI R package for proficient automatic profiling of 1D <Superscript>1</Superscript>H-NMR spectra of study datasets

Introduction

Adoption of automatic profiling tools for ¹H-NMR-based metabolomic studies still lags behind other approaches in the absence of the flexibility and interactivity necessary to adapt to the properties of study data sets of complex matrices.

Objectives

To provide an open source tool that fully integrates these needs and enables the reproducibility of the profiling process.

Methods

rDolphin incorporates novel techniques to optimize exploratory analysis, metabolite identification, and validation of profiling output quality.

Results

The information and quality achieved in two public datasets of complex matrices are maximized.

Conclusion

rDolphin is an open-source R package (http://github.com/danielcanueto/rDolphin) able to provide the best balance between accuracy, reproducibility and ease of use.