Sketching algorithms for genomic data analysis and querying in a secure enclave.

Genome-wide association studies (GWAS), especially on rare diseases, may necessitate exchange of sensitive genomic data between multiple institutions. Since genomic data sharing is often infeasible due to privacy concerns, cryptographic methods, such as secure multiparty computation (SMC) protocols, have been developed with the aim of offering privacy-preserving collaborative GWAS. Unfortunately, the computational overhead of these methods remain prohibitive for human-genome-scale data. Here we introduce SkSES (https://github.com/ndokmai/sgx-genome-variants-search), a hardware-software hybrid approach for privacy-preserving collaborative GWAS, which improves the running time of the most advanced cryptographic protocols by two orders of magnitude. The SkSES approach is based on trusted execution environments (TEEs) offered by current-generation microprocessors-in particular, Intel's SGX. To overcome the severe memory limitation of the TEEs, SkSES employs novel 'sketching' algorithms that maintain essential statistical information on genomic variants in input VCF files. By additionally incorporating efficient data compression and population stratification reduction methods, SkSES identifies the top k genomic variants in a cohort quickly, accurately and in a privacy-preserving manner.

A System Architecture for Efficient Transmission of Massive DNA Sequencing Data.

The DNA sequencing data analysis pipelines require significant computational resources. In that sense, cloud computing infrastructures appear as a natural choice for this processing. However, the first practical difficulty in reaching the cloud computing services is the transmission of the massive DNA sequencing data from where they are produced to where they will be processed. The daily practice here begins with compressing the data in FASTQ file format, and then sending these data via fast data transmission protocols. In this study, we address the weaknesses in that daily practice and present a new system architecture that incorporates the computational resources available on the client side while dynamically adapting itself to the available bandwidth. Our proposal considers the real-life scenarios, where the bandwidth of the connection between the parties may fluctuate, and also the computing power on the client side may be of any size ranging from moderate personal computers to powerful workstations. The proposed architecture aims at utilizing both the communication bandwidth and the computing resources for satisfying the ultimate goal of reaching the results as early as possible. We present a prototype implementation of the proposed architecture, and analyze several real-life cases, which provide useful insights for the sequencing centers, especially on deciding when to use a cloud service and in what conditions.

Evaluation of halitosis using OralChroma™ in patients with allergic rhinitis.

OBJECTIVE: The objective of this study was to evaluate the occurrence of halitosis in patients with allergic rhinitis (AR). MATERIALS AND METHODS: In this study, we enrolled 53 patients with AR and 34 participants as controls. Halitosis was evaluated by measuring volatile sulphur compound (VSC) levels. VSCs, which consist of hydrogen sulphide (HS), methyl mercaptan (MM), and dimethyl sulphide (DMS), were measured using a portable gas chromatograph (OralChroma™; AbiMedical, Osaka, Japan). RESULTS: Patients with AR exhibited significantly higher levels of MM and DMS that did control subjects. Specifically, MM levels showed a greater increase than DMS levels in patients with AR than in controls. We observed no significant changes in the levels of HS between the groups. CONCLUSION: This study demonstrated that AR is likely to result in halitosis. Several studies have overlooked the relationship between halitosis and AR. In light of our results, we suggest that halitosis should be further investigated in patients with AR.

Robustness of Massively Parallel Sequencing Platforms.

The improvements in high throughput sequencing technologies (HTS) made clinical sequencing projects such as ClinSeq and Genomics England feasible. Although there are significant improvements in accuracy and reproducibility of HTS based analyses, the usability of these types of data for diagnostic and prognostic applications necessitates a near perfect data generation. To assess the usability of a widely used HTS platform for accurate and reproducible clinical applications in terms of robustness, we generated whole genome shotgun (WGS) sequence data from the genomes of two human individuals in two different genome sequencing centers. After analyzing the data to characterize SNPs and indels using the same tools (BWA, SAMtools, and GATK), we observed significant number of discrepancies in the call sets. As expected, the most of the disagreements between the call sets were found within genomic regions containing common repeats and segmental duplications, albeit only a small fraction of the discordant variants were within the exons and other functionally relevant regions such as promoters. We conclude that although HTS platforms are sufficiently powerful for providing data for first-pass clinical tests, the variant predictions still need to be confirmed using orthogonal methods before using in clinical applications.

Acoustic, perceptual and aerodynamic voice evaluation in an obese population.

OBJECTIVE: To investigate perceptual, acoustic and aerodynamic voice parameters in obese individuals. METHODS: Twenty obese and 20 normal-weight volunteers underwent voice evaluation by laryngoscopy, acoustic analysis, aerodynamic measurement and perceptual analysis (using the grade-roughness-breathiness-asthenia-strain ('GRBAS') scale and the Voice Handicap Index 10 scale). Data from both subject groups were compared. RESULTS: No difference was found in acoustic analysis parameters between the two groups (p > 0.05). Maximum phonation time in the obese group (mean ± standard deviation, 19.6 ± 4.9 seconds) was significantly shorter than in controls (26.4 ± 4.1 seconds) (p < 0.001), although the s/z ratio was very similar between the two groups. In the obese and control groups, the mean ± standard deviation grade-roughness-breathiness-asthenia-strain scores were 1 ± 1.3 and 0.2 ± 0.6 (p = 0.002) and the mean ± standard deviation Voice Handicap Index 10 scores were 0.5 ± 1.2 and 1.2 ± 1.7 (p = 0.27), respectively. CONCLUSION: Obese individuals had poorer vocal quality as judged by the grade-roughness-breathiness-asthenia-strain scale, and reduced maximum phonation time. However, there was no change in voice quality as assessed by acoustic analysis and Vocal Handicap Index 10 score, compared with controls.

Efficient maximal repeat finding using the burrows-wheeler transform and wavelet tree.

Finding repetitive structures in genomes and proteins is important to understand their biological functions. Many data compressors for modern genomic sequences rely heavily on finding repeats in the sequences. The notion of maximal repeats captures all the repeats in the data in a space-efficient way. Prior work on maximal repeat finding used either a suffix tree or a suffix array along with other auxiliary data structures. Their space usage is 19--50 times the text size with the best engineering efforts, prohibiting their usability on massive data. Our technique uses the Burrows-Wheeler Transform and wavelet trees. For data sets consisting of natural language texts, the space usage of our method is no more than three times the text size. For genomic sequences stored using one byte per base, the space usage is less than double the sequence size. Our method is also orders of magnitude faster than the prior methods for processing massive texts, since the prior methods must use external memory. For the first time, our method enables a desktop computer with 8GB internal memory to find all the maximal repeats in the whole human genome in less than 17 hours. We have implemented our method as general-purpose open-source software for public use.

Ψ-RA: a parallel sparse index for genomic read alignment.

BACKGROUND: Genomic read alignment involves mapping (exactly or approximately) short reads from a particular individual onto a pre-sequenced reference genome of the same species. Because all individuals of the same species share the majority of their genomes, short reads alignment provides an alternative and much more efficient way to sequence the genome of a particular individual than does direct sequencing. Among many strategies proposed for this alignment process, indexing the reference genome and short read searching over the index is a dominant technique. Our goal is to design a space-efficient indexing structure with fast searching capability to catch the massive short reads produced by the next generation high-throughput DNA sequencing technology. RESULTS: We concentrate on indexing DNA sequences via sparse suffix arrays (SSAs) and propose a new short read aligner named Ψ-RA (PSI-RA: parallel sparse index read aligner). The motivation in using SSAs is the ability to trade memory against time. It is possible to fine tune the space consumption of the index based on the available memory of the machine and the minimum length of the arriving pattern queries. Although SSAs have been studied before for exact matching of short reads, an elegant way of approximate matching capability was missing. We provide this by defining the rightmost mismatch criteria that prioritize the errors towards the end of the reads, where errors are more probable. Ψ-RA supports any number of mismatches in aligning reads. We give comparisons with some of the well-known short read aligners, and show that indexing a genome with SSA is a good alternative to the Burrows-Wheeler transform or seed-based solutions. CONCLUSIONS: Ψ-RA is expected to serve as a valuable tool in the alignment of short reads generated by the next generation high-throughput sequencing technology. Ψ-RA is very fast in exact matching and also supports rightmost approximate matching. The SSA structure that Ψ-RA is built on naturally incorporates the modern multicore architecture and thus further speed-up can be gained. All the information, including the source code of Ψ-RA, can be downloaded at: http://www.busillis.com/o_kulekci/PSIRA.zip.

Intratympanic methylprednisolone injections for subjective tinnitus.

OBJECTIVES: This study aimed to determine whether intratympanically injected methylprednisolone is effective in treating subjective tinnitus refractory to medical treatment. STUDY DESIGN: Prospective, randomised, placebo-controlled, single-blinded study. METHODS: Seventy adult patients with subjective tinnitus of cochlear origin were randomly assigned to receive intratympanic injection of either methylprednisolone or saline solution. The treatment protocol comprised three intratympanic injections, one per week for three weeks. Improvement in tinnitus severity was measured by a self-rated tinnitus loudness scale and by the tinnitus severity index, at baseline and two weeks after the last injection. RESULTS: Data for 59 patients were available for analysis. There was no significant difference between the two treatment groups regarding age, sex, pure tone average, pretreatment tinnitus intensity, tinnitus laterality or tinnitus duration. There was a significant post-treatment improvement in self-rated tinnitus loudness scale results in both groups. No significant post-treatment changes in the tinnitus severity index individual and total scores were observed in either group. The most frequently encountered side effects were pain during injection, vertigo, a burning sensation around the ear and in the throat, and a bitter taste. A burning sensation and bitter taste were observed more often in the methylprednisolone group compared with the placebo group. CONCLUSION: The results of this study indicate that intratympanic methylprednisolone has no benefit, compared with placebo, for the treatment of subjective tinnitus of cochlear origin refractory to medical treatment.