The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Social Network Analysis

Since the completion of the human genome project in 2003, extraordinary progress has been made in genome sequencing technologies, which has led to a decreased cost per megabase and an increase in the number and diversity of sequenced genomes. An astonishing complexity of genome architecture has been revealed, bringing these sequencing technologies to even greater advancements. Some approaches maximize the number of bases sequenced in the least amount of time, generating a wealth of data that can be used to understand increasingly complex phenotypes. Alternatively, other approaches now aim to sequence longer contiguous pieces of DNA, which are essential for resolving structurally complex regions. These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.

Coming of age: ten years of next-generation sequencing technologies

While metagenomics has emerged as a technology of choice for analyzing bacterial populations, the assembly of metagenomic data remains challenging, thus stifling biological discoveries. Moreover, recent studies revealed that complex bacterial populations may be composed from dozens of related strains, thus further amplifying the challenge of metagenomic assembly. metaSPAdes addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes. We benchmark metaSPAdes against other state-of-the-art metagenome assemblers and demonstrate that it results in high-quality assemblies across diverse data sets.

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MetaSPAdes: A new versatile metagenomic assembler

Here we present deep-learning techniques for healthcare, centering our discussion on deep learning in computer vision, natural language processing, reinforcement learning, and generalized methods. We describe how these computational techniques can impact a few key areas of medicine and explore how to build end-to-end systems. Our discussion of computer vision focuses largely on medical imaging, and we describe the application of natural language processing to domains such as electronic health record data. Similarly, reinforcement learning is discussed in the context of robotic-assisted surgery, and generalized deep-learning methods for genomics are reviewed.

A guide to deep learning in healthcare.

Although many algorithms for the multi-armed bandit problem are well-understood theoretically, empirical confirmation of their effectiveness is generally scarce. This paper presents a thorough empirical study of the most popular multi-armed bandit algorithms. Three important observations can be made from our results. Firstly, simple heuristics such as epsilon-greedy and Boltzmann exploration outperform theoretically sound algorithms on most settings by a significant margin. Secondly, the performance of most algorithms varies dramatically with the parameters of the bandit problem. Our study identifies for each algorithm the settings where it performs well, and the settings where it performs poorly. Thirdly, the algorithms' performance relative each to other is affected only by the number of bandit arms and the variance of the rewards. This finding may guide the design of subsequent empirical evaluations. In the second part of the paper, we turn our attention to an important area of application of bandit algorithms: clinical trials. Although the design of clinical trials has been one of the principal practical problems motivating research on multi-armed bandits, bandit algorithms have never been evaluated as potential treatment allocation strategies. Using data from a real study, we simulate the outcome that a 2001-2002 clinical trial would have had if bandit algorithms had been used to allocate patients to treatments. We find that an adaptive trial would have successfully treated at least 50% more patients, while significantly reducing the number of adverse effects and increasing patient retention. At the end of the trial, the best treatment could have still been identified with a high level of statistical confidence. Our findings demonstrate that bandit algorithms are attractive alternatives to current adaptive treatment allocation strategies.

Algorithms for multi-armed bandit problems.

Methods for reasoning under uncertainty are a key building block of accurate and reliable machine learning systems. Bayesian methods provide a general framework to quantify uncertainty. However, because of model misspecification and the use of approximate inference, Bayesian uncertainty estimates are often inaccurate -- for example, a 90% credible interval may not contain the true outcome 90% of the time. Here, we propose a simple procedure for calibrating any regression algorithm; when applied to Bayesian and probabilistic models, it is guaranteed to produce calibrated uncertainty estimates given enough data. Our procedure is inspired by Platt scaling and extends previous work on classification. We evaluate this approach on Bayesian linear regression, feedforward, and recurrent neural networks, and find that it consistently outputs well-calibrated credible intervals while improving performance on time series forecasting and model-based reinforcement learning tasks.

/pdf/accurate-uncertainties-for-deep-learning-using-calibrated-2i0kqlvv5y.pdf

Accurate Uncertainties for Deep Learning Using Calibrated Regression.

Haplotyping of human genomes is improved by augmenting experimental dilution-based haplotyping with statistical analyses, a strategy known until now only as 'Moleculo.'

/pdf/whole-genome-haplotyping-using-long-reads-and-statistical-22vzr7uqlp.pdf

Volodymyr Kuleshov

Papers

A guide to deep learning in healthcare.

Algorithms for multi-armed bandit problems.

Accurate Uncertainties for Deep Learning Using Calibrated Regression.

Whole-genome haplotyping using long reads and statistical methods

Accurate Uncertainties for Deep Learning Using Calibrated Regression