MOTIVATION: Double minute (DM) chromosomes are acentric extrachromosomal DNA artifacts that are frequently observed in the cells of numerous cancers. They are highly amplified and contain oncogenes and drug-resistance genes, making their presence a challenge for effective cancer treatment. Algorithmic discovery of DM can potentially improve bench-derived therapies for cancer treatment. A hindrance to this task is that DMs evolve, yielding circular chromatin that shares segments from progenitor DMs. This creates DMs with overlapping amplicon coordinates. Existing DM discovery algorithms use whole genome shotgun sequencing (WGS) in isolation, which can potentially incorrectly classify DMs that share overlapping coordinates. RESULTS: In this study, we describe an algorithm called 'HolistIC' that can predict DMs in tumor genomes by integrating WGS and Hi-C sequencing data. The consolidation of these sources of information resolves ambiguity in DM amplicon prediction that exists in DM prediction with WGS data used in isolation. We implemented and tested our algorithm on the tandem Hi-C and WGS datasets of three cancer datasets and a simulated dataset. Results on the cancer datasets demonstrated HolistIC's ability to predict DMs from Hi-C and WGS data in tandem. The results on the simulated data showed the HolistIC can accurately distinguish DMs that have overlapping amplicon coordinates, an advance over methods that predict extrachromosomal amplification using WGS data in isolation. AVAILABILITY AND IMPLEMENTATION: Our software, named 'HolistIC', is available at http://www.github.com/mhayes20/HolistIC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Entity linking is the task of mapping potentially ambiguous terms in text to their constituent entities in a knowledge base like Wikipedia. This is useful for organizing content, extracting structured data from textual documents, and in machine learning relevance applications like semantic search, knowledge graph construction, and question answering. Traditionally, this work has focused on text that has been well-formed, like news articles, but in common real world datasets such as messaging, resumes, or short-form social media, non-grammatical, loosely-structured text adds a new dimension to this problem. This paper presents Pangloss, a production system for entity disambiguation on noisy text. Pangloss combines a probabilistic linear-time key phrase identification algorithm with a semantic similarity engine based on context-dependent document embeddings to achieve better than state-of-the-art results (>5% in F1) compared to other research or commercially available systems. In addition, Pangloss leverages a local embedded database with a tiered architecture to house its statistics and metadata, which allows rapid disambiguation in streaming contexts and on-device disambiguation in low-memory environments such as mobile phones.

BACKGROUND: Genomic structural variants (SV) play a significant role in the onset and progression of cancer. Genomic deletions can create oncogenic fusion genes or cause the loss of tumor suppressing gene function which can lead to tumorigenesis by downregulating these genes. Detecting these variants has clinical importance in the treatment of diseases. Furthermore, it is also clinically important to detect their breakpoint boundaries at high resolution. We have generalized the framework of a previously-published algorithm that located translocations, and we have applied that framework to develop a method to locate deletions at base pair level using next-generation sequencing data. Our method uses abnormally mapped read pairs, and then subsequently maps split reads to identify precise breakpoints. RESULTS: On a primary prostate cancer dataset and a simulated dataset, our method predicted the number, type, and breakpoints of biologically validated SVs at high accuracy. It also outperformed two existing algorithms on precise breakpoint prediction, which is clinically important. CONCLUSION: Our algorithm, called Pegasus, accurately calls deletion breakpoints. However, the method must be extended to allow for germline variant filtering and heterozygous deletion detection. The source code that implements Pegasus can be downloaded from the following URL: http://github.com/mhayes20/Pegasus .

Software Defined Networking (SDN) is an innovative approach to networking architecture that opens up avenues to create a whole new class of networking functionality. While data centre networks are steadily adopting the SDN approach with considerable success, other areas of networking such as network access control, load balancing and traffic classification remain nascent. Traffic classification in SDN is relatively experimental and attempts for SDN traffic classification to become a viable solution for enterprise networks require additional investigation. This paper reports on the practical experiences and lessons learned while developing an SDN based traffic classification platform for an enterprise network. We use the platform to demonstrate the feasibility of SDN based traffic classifiers by evaluating against a set of desired outcomes. We make note of the design choices using the currently available technologies that may be helpful to networks operators considering deploying their own solution. We conclude the paper with suggested changes to better address limitations for software traffic classification that will remove the need for workarounds with future versions of OpenFlow.

"Skills and Expertise" is a data-driven feature on LinkedIn, the world's largest professional online social network, which allows members to tag themselves with topics representing their areas of expertise. In this work, we present our experiences developing this large-scale topic extraction pipeline, which includes constructing a folksonomy of skills and expertise and implementing an inference and recommender system for skills. We also discuss a consequent set of applications, such as Endorsements, which allows members to tag themselves with topics representing their areas of expertise and for their connections to provide social proof, via an "endorse" action, of that member's competence in that topic.

Hadoop enables processing of large data sets through its relatively easy-to-use semantics. However, jobs are often written inefficiently for tasks that could be computed incrementally due to the burdensome incremental state management for the programmer. This paper introduces Hourglass, a library for developing incremental monoid computations on Hadoop. It runs on unmodified Hadoop and provides an accumulator-based interface for programmers to store and use state across successive runs; the framework ensures that only the necessary subcomputations are performed. It is successfully used at LinkedIn, one of the largest online social networks, for many use cases in dashboarding and machine learning. Hourglass is open source and freely available.

MOTIVATION: For many complex traits/diseases, it is believed that rare variants account for some of the missing heritability that cannot be explained by common variants. Sequencing a large number of samples through DNA pooling is a cost-effective strategy to discover rare variants and to investigate their associations with phenotypes. Overlapping pool designs provide further benefit because such approaches can potentially identify variant carriers, which is important for downstream applications of association analysis of rare variants. However, existing algorithms for analysing sequence data from overlapping pools are limited. RESULTS: We propose a complete data analysis framework for overlapping pool designs, with novelties in all three major steps: variant pool and variant locus identification, variant allele frequency estimation and variant sample decoding. The framework can be used in combination with any design matrix. We have investigated its performance based on two different overlapping designs and have compared it with three state-of-the-art methods, by simulating targeted sequencing and by pooling real sequence data. Results on both datasets show that our algorithm has made significant improvements over existing ones. In conclusion, successful discovery of rare variants and identification of variant carriers using overlapping pool strategies critically depend on many steps, from generation of design matrixes to decoding algorithms. The proposed framework in combination with the design matrixes generated based on the Chinese remainder theorem achieves best overall results. AVAILABILITY: Source code of the program, termed VIP for Variant Identification by Pooling, is available at http://cbc.case.edu/VIP.

BACKGROUND: Somatically-acquired translocations may serve as important markers for assessing the cause and nature of diseases like cancer. Algorithms to locate translocations may use next-generation sequencing (NGS) platform data. However, paired-end strategies do not accurately predict precise translocation breakpoints, and "split-read" methods may lose sensitivity if a translocation boundary is not captured by many sequenced reads. To address these challenges, we have developed "Bellerophon", a method that uses discordant read pairs to identify potential translocations, and subsequently uses "soft-clipped" reads to predict the location of the precise breakpoints. Furthermore, for each chimeric breakpoint, our method attempts to classify it as a participant in an unbalanced translocation, balanced translocation, or interchromosomal insertion. RESULTS: We compared Bellerophon to four previously published algorithms for detecting structural variation (SV). Using two simulated datasets and two prostate cancer datasets, Bellerophon had overall better performance than the other methods. Furthermore, our method accurately predicted the presence of the interchromosomal insertions placed in our simulated dataset, which is an ability that the other SV prediction programs lack. CONCLUSIONS: The combined use of paired reads and soft-clipped reads allows Bellerophon to detect interchromosomal breakpoints with high sensitivity, while also mitigating losses in specificity. This trend is seen across all datasets examined. Because it does not perform assembly on soft-clipped subreads, Bellerophon may be limited in experiments where sequence read lengths are short. AVAILABILITY: The program can be downloaded from http://cbc.case.edu/Bellerophon.

A full-rate and full-diversity closed-loop quasi-orthogonal space time block coding scheme pioneered by Toker, Lambotharan and Chambers is proposed for application in virtual antenna arrays. The theoretical capacity and throughput gains are evaluated as a function of signal-to-noise ratio. It is shown that the scheme has particular benefits in both ergodic and non-ergodic channel environments, and outperforms virtual antenna arrays based solely upon conventional orthogonal space time block codes.

A full rate and full diversity closed-loop quasi-orthogonal space time block coding scheme due to Toker, Lambotharan and Chambers is proposed for application in virtual antenna arrays. The performance gain is achieved through closed-loop operation involving feedback of phase rotation angle(s) calculated from channel state information (CSI) to the transmitter array. Throughput performance of the proposed scheme, with and without power optimisation, is investigated through Monte Carlo simulation with QPSK constellation signals. The results confirm the improvement in throughput performance over orthogonal space time block codes.