FPGA acceleration of reference-based compression for genomic data

One of the key challenges facing genomics today is efficiently storing the massive amounts of data generated by next-generation sequencing platforms. Reference-based compression is a popular strategy for reducing the size of genomic data, whereby sequence information is encoded as a mapping to a known reference sequence. Determining the mapping is a computationally intensive problem, and is the bottleneck of most reference-based compression tools currently available. This paper presents the first FPGA acceleration of reference-based compression for genomic data. We develop a new mapping algorithm based on the FM-index search operation which includes optimisations targeting the compression ratio and speed. Our hardware design is implemented on a Maxeler MPC-X2000 node comprising 8 Altera Stratix V FPGAs. When evaluated against compression tools currently available, our tool achieves a superior compression ratio, compression time, and energy consumption for both FASTA and FASTQ formats. For example, our tool achieves a 30% higher compression ratio and is 71.9 times faster than the fastqz tool

Phantom evaluation of a cardiac SPECT/VCT system that uses a common set of solid-state detectors for both emission and transmission scans

We developed a cardiac SPECT system (X-ACT) with low dose volume CT transmission-based attenuation correction (AC). Three solid-state detectors are configured to form a triple-head system for emission scans and reconfigured to form a 69-cm field-of-view detector arc for transmission scans. A near mono-energetic transmission line source is produced from the collimated fluorescence x-ray emitted from a lead target when the target is illuminated by a narrow polychromatic x-ray beam from an x-ray tube. Transmission scans can be completed in 1 min with insignificant patient dose (deep dose equivalent <5 μSv). We used phantom studies to evaluate (1) the accuracy of the reconstructed attenuation maps, (2) the effect of AC on image uniformity, and (3) the effect of AC on defect contrast (DC). The phantoms we used included an ACR phantom, an anthropomorphic phantom with a uniform cardiac insert, and an anthropomorphic phantom with two defects in the cardiac insert. The reconstructed attenuation coefficient of water at 140 keV was .150 ± .003/cm in the uniform region of the ACR phantom, .151 ± .003/cm and .151 ± .002/cm in the liver and cardiac regions of the anthropomorphic phantom. The ACR phantom images with AC showed correction of the bowing effect due to attenuation in the images without AC (NC). The 17-segment scores of the images of the uniform cardiac insert were 78.3 ± 6.5 before and 87.9 ± 3.3 after AC (average ± standard deviation). The inferior-to-anterior wall ratio and the septal-to-lateral wall ratio were .99 and 1.16 before and 1.02 and 1.00 after AC. The DC of the two defects was .528 and .156 before and .628 and .173 after AC. The X-ACT system generated accurate attenuation maps with 1-minute transmission scans. AC improved image quality and uniformity over NC

Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): a multicentre, blinded-endpoint, phase 4, randomised controlled trial

Background The optimal timing of anticoagulation for patients with acute ischaemic stoke with atrial fibrillation is uncertain. We investigated the efficacy and safety of early compared with delayed initiation of direct oral anticoagulants (DOACs) in patients with acute ischaemic stroke associated with atrial fibrillation. Methods We performed a multicentre, open-label, blinded-endpoint, parallel-group, phase 4, randomised controlled trial at 100 UK hospitals. Adults with atrial fibrillation and a clinical diagnosis of acute ischaemic stroke and whose physician was uncertain of the optimal timing for DOAC initiation were eligible for inclusion in the study. We randomly assigned participants (1:1) to early (ie, ≤4 days from stroke symptom onset) or delayed (ie, 7–14 days) anticoagulation initiation with any DOAC, using an independent online randomisation service with random permuted blocks and varying block length, stratified by stroke severity at randomisation. Participants and treating clinicians were not masked to treatment assignment, but all outcomes were adjudicated by a masked independent external adjudication committee using all available clinical records, brain imaging reports, and source images. The primary outcome was a composite of recurrent ischaemic stroke, symptomatic intracranial haemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days in a modified intention-to-treat population. We used a gatekeeper approach by sequentially testing for a non-inferiority margin of 2 percentage points, followed by testing for superiority. OPTIMAS is registered with ISRCTN (ISRCTN17896007) and ClinicalTrials.gov (NCT03759938), and the trial is ongoing. FindingsBetween July 5, 2019, and Jan 31, 2024, 3648 patients were randomly assigned to early or delayed DOAC initiation. 27 participants did not fulfil the eligibility criteria or withdrew consent to include their data, leaving 3621 patients (1814 in the early group and 1807 in the delayed group; 1981 men and 1640 women) in the modified intention-to-treat analysis. The primary outcome occurred in 59 (3·3%) of 1814 participants in the early DOAC initiation group compared with 59 (3·3%) of 1807 participants in the delayed DOAC initiation group (adjusted risk difference [RD] 0·000, 95% CI –0·011 to 0·012). The upper limit of the 95% CI for the adjusted RD was less than the non-inferiority margin of 2 percentage points (pnon-inferiority =0·0003). Superiority was not identified (psuperiority =0·96). Symptomatic intracranial haemorrhage occurred in 11 (0·6%) participants allocated to the early DOAC initiation group compared with 12 (0·7%) participants allocated to the delayed DOAC initiation group (adjusted RD 0·001, –0·004 to 0·006; p=0·78). Interpretation Early DOAC initiation within 4 days after ischaemic stroke associated with atrial fibrillation was noninferior to delayed initiation for the composite outcome of ischaemic stroke, intracranial haemorrhage, unclassifiable stroke, or systemic embolism at 90 days. Our findings do not support the current common and guideline-supported practice of delaying DOAC initiation after ischaemic stroke with atrial fibrillation

Leveraging FPGAS for accelerating short read alignment

One of the key challenges facing genomics today is how to efficiently analyze the massive amounts of data produced by next-generation sequencing platforms. With general-purpose computing systems struggling to address this challenge, specialized processors such as the Field-Programmable Gate Array (FPGA) are receiving growing interest. The means by which to leverage this technology for accelerating genomic data analysis is however largely unexplored. In this paper, we present a runtime reconfigurable architecture for accelerating short read alignment using FPGAS. This architecture exploits the reconfigurability of FPGAS to allow the development of fast yet flexible alignment designs. We apply this architecture to develop an alignment design which supports exact and approximate alignment with up to two mismatches. Our design is based on the FM-index, with optimizations to improve the alignment performance. In particular, the $n$ -step FM-index, index oversampling, a seed-and-compare stage, and bi-directional backtracking are included. Our design is implemented and evaluated on a 1U Maxeler MPC-X2000 dataflow node with eight Altera Stratix-V FPGAS. Measurements show that our design is 28 times faster than Bowtie2 running with 16 threads on dual Intel Xeon E5-2640 CPUs, and nine times faster than Soap3-dp running on an NVIDIA Tesla C2070 GPU

Dfesnippets: An open-source library for dataflow acceleration on FPGAs

Highly-tuned FPGA implementations can achieve significant performance and power efficiency gains over general purpose hardware. However the limited development productivity has prevented mainstream adoption of FPGAs in many areas such as High Performance Computing. High level standard development libraries are increasingly adopted in improving productivity. We propose an approach for performance critical applications including standard library modules, benchmarking facilities and application benchmarks to support a variety of usecases. We implement the proposed approach as an open-source library for a commercially available FPGA system and highlight applications and productivity gains

GeDi: applying su x arrays to increase the repertoire of detectable SNVs in tumour genomes

Background Current popular variant calling pipelines rely on the mapping coordinates of each input read to a reference genome in order to detect variants. Since reads deriving from variant loci that diverge in sequence substantially from the reference are often assigned incorrect mapping coordinates, variant calling pipelines that rely on mapping coordinates can exhibit reduced sensitivity. Results In this work we present GeDi, a suffix array-based somatic single nucleotide variant (SNV) calling algorithm that does not rely on read mapping coordinates to detect SNVs and is therefore capable of reference-free and mapping-free SNV detection. GeDi executes with practical runtime and memory resource requirements, is capable of SNV detection at very low allele frequency (<1%), and detects SNVs with high sensitivity at complex variant loci, dramatically outperforming MuTect, a well-established pipeline. Conclusion By designing novel suffix-array based SNV calling methods, we have developed a practical SNV calling software, GeDi, that can characterise SNVs at complex variant loci and at low allele frequency thus increasing the repertoire of detectable SNVs in tumour genomes. We expect GeDi to find use cases in targeted-deep sequencing analysis, and to serve as a replacement and improvement over previous suffix-array based SNV calling methods

Superior semi-circular canal dehiscence syndrome: quantifying the effectiveness of treatment from the patient's perspective

AbstractBackgroundSuperior semi-circular canal dehiscence syndrome is a disorder characterised by auditory and vestibular symptoms that can significantly impact quality of life, and yet it has no disease-specific quality of life instrument.MethodThirty-six patients who underwent transmastoid superior semicircular canal resurfacing and plugging were included from an initial cohort of 60 surgically managed patients. A sub-cohort of 19 consecutive patients completed validated symptom and quality of life questionnaires before and after surgery. Of the 36 patients, 31 participated in a telephone semi-structured interview post-operatively.ResultsFollowing surgery, there was a statistically significant improvement in autophony index score (p = 0.02), symptom severity score (p &lt; 0.001) and sound hypersensitivity (p = 0.01). Thematic analysis of telephone interviews suggested three main symptom themes: auditory hypersensitivity, dysequilibrium, headache and concentration difficulties. Dysequilibrium was found to persist post-operatively.ConclusionSurgery improves overall symptoms and quality of life. However, important symptom themes may be overlooked using the outcome measures that are currently available. A unified disease-specific outcome measure is urgently required to better understand the impact of symptoms and measure treatment effects.</jats:sec