A comprehensive and scalable database search system for metaproteomics.

BACKGROUND: Mass spectrometry-based shotgun proteomics experiments rely on accurate matching of experimental spectra against a database of protein sequences. Existing computational analysis methods are limited in the size of their sequence databases, which severely restricts the proteomic sequencing depth and functional analysis of highly complex samples. The growing amount of public high-throughput sequencing data will only exacerbate this problem. We designed a broadly applicable metaproteomic analysis method (ComPIL) that addresses protein database size limitations. RESULTS: Our approach to overcome this significant limitation in metaproteomics was to design a scalable set of sequence databases assembled for optimal library querying speeds. ComPIL was integrated with a modified version of the search engine ProLuCID (termed "Blazmass") to permit rapid matching of experimental spectra. Proof-of-principle analysis of human HEK293 lysate with a ComPIL database derived from high-quality genomic libraries was able to detect nearly all of the same peptides as a search with a human database (~500x fewer peptides in the database), with a small reduction in sensitivity. We were also able to detect proteins from the adenovirus used to immortalize these cells. We applied our method to a set of healthy human gut microbiome proteomic samples and showed a substantial increase in the number of identified peptides and proteins compared to previous metaproteomic analyses, while retaining a high degree of protein identification accuracy and allowing for a more in-depth characterization of the functional landscape of the samples. CONCLUSIONS: The combination of ComPIL with Blazmass allows proteomic searches to be performed with database sizes much larger than previously possible. These large database searches can be applied to complex meta-samples with unknown composition or proteomic samples where unexpected proteins may be identified. The protein database, proteomic search engine, and the proteomic data files for the 5 microbiome samples characterized and discussed herein are open source and available for use and additional analysis.

Privacy and security in the era of digital health: what should translational researchers know and do about it?

The rapid growth in the availability and incorporation of digital technologies in almost every aspect of our lives creates extraordinary opportunities but brings with it unique challenges. This is especially true for the translational researcher, whose work has been markedly enhanced through the capabilities of big data aggregation and analytics, wireless sensors, online study enrollment, mobile engagement, and much more. At the same time each of these tools brings distinctive security and privacy issues that most translational researchers are inadequately prepared to deal with despite accepting overall responsibility for them. For the researcher, the solution for addressing these challenges is both simple and complex. Cyber-situational awareness is no longer a luxury-it is fundamental in combating both the elite and highly organized adversaries on the Internet as well as taking proactive steps to avoid a careless turn down the wrong digital dark alley. The researcher, now responsible for elements that may/may not be beyond his or her direct control, needs an additional level of cyber literacy to understand the responsibilities imposed on them as data owner. Responsibility lies with knowing what you can do about the things you can control and those you can't. The objective of this paper is to describe the data privacy and security concerns that translational researchers need to be aware of, and discuss the tools and techniques available to them to help minimize that risk.

Omics Pipe: a community-based framework for reproducible multi-omics data analysis.

MOTIVATION: Omics Pipe (http://sulab.scripps.edu/omicspipe) is a computational framework that automates multi-omics data analysis pipelines on high performance compute clusters and in the cloud. It supports best practice published pipelines for RNA-seq, miRNA-seq, Exome-seq, Whole-Genome sequencing, ChIP-seq analyses and automatic processing of data from The Cancer Genome Atlas (TCGA). Omics Pipe provides researchers with a tool for reproducible, open source and extensible next generation sequencing analysis. The goal of Omics Pipe is to democratize next-generation sequencing analysis by dramatically increasing the accessibility and reproducibility of best practice computational pipelines, which will enable researchers to generate biologically meaningful and interpretable results. RESULTS: Using Omics Pipe, we analyzed 100 TCGA breast invasive carcinoma paired tumor-normal datasets based on the latest UCSC hg19 RefSeq annotation. Omics Pipe automatically downloaded and processed the desired TCGA samples on a high throughput compute cluster to produce a results report for each sample. We aggregated the individual sample results and compared them to the analysis in the original publications. This comparison revealed high overlap between the analyses, as well as novel findings due to the use of updated annotations and methods. AVAILABILITY AND IMPLEMENTATION: Source code for Omics Pipe is freely available on the web (https://bitbucket.org/sulab/omics_pipe). Omics Pipe is distributed as a standalone Python package for installation (https://pypi.python.org/pypi/omics_pipe) and as an Amazon Machine Image in Amazon Web Services Elastic Compute Cloud that contains all necessary third-party software dependencies and databases (https://pythonhosted.org/omics_pipe/AWS_installation.html).

Multisensory spatial representations in eye-centered coordinates for reaching.

Humans can reach for objects with their hands whether the objects are seen, heard or touched. Thus, the position of objects is recoded in a joint-centered frame of reference regardless of the sensory modality involved. Our study indicates that this frame of reference is not the only one shared across sensory modalities. The location of reaching targets is also encoded in eye-centered coordinates, whether the targets are visual, auditory, proprioceptive or imaginary. Furthermore, the remembered eye-centered location is updated after each eye and head movement. This is quite surprising since, in principle, a reaching motor command can be computed from any non-visual modality without ever recovering the eye-centered location of the stimulus. This finding may reflect the predominant role of vision in human spatial perception.