Comparison of CPU and Parabricks GPU Enabled Bioinformatics Software for High Throughput Clinical Genomic Applications

In recent years, high performance computing (HPC) has begun to revolutionize the architecture of software and servers to meet the ever-increasing demand for speed & efficiency. One of the ways this change is manifesting is the adoption of graphics processor units (GPUs). Used correctly, GPUS can increase throughput and decrease compute time for certain computational problems. Bioinformatics, an HPC dependent discipline, is no exception. As bioinformatics continues advance clinical care by sequencing patient’s DNA and RNA for diagnosis of diseases, there is an ever-increasing demand for faster data processing to improve clinical sequencing turnaround time. Parabricks, a GPU enabled bioinformatics software is one of the leaders in ‘lifting over’ common CPU bioinformatics tools to GPU architectures. In the present study, bioinformatics pipelines built with Parabricks GPU enabled software are compared with standard CPU bioinformatics software. Pipeline results and run performance comparisons are performed to show the impact this technology change can have for a medium sized computational cluster. The present study finds that Parabricks’ GPU workflows show a massive increase in overall efficiency by cutting overall run time by roughly 21x, cutting overall computational hours needed by 650x. Parabricks GPU workflows show a 99.5% variant call concordance rate when compared to clinically validated CPU workflows. Substitution of Parabricks GPU alignment into a clinically validated CPU based pipeline reduces the number of compute hours from 836 hours to 727 hours and returns the same results, showing CPU and GPU’s can be used together to reduce pipeline turnaround time & compute resource burden. Overall, integration of GPUs into bioinformatic pipelines leads to massive reduction of turnaround time, reduction of computation times, and increased throughput, with little to no sacrifice in overall output quality. The findings of this study show GPU based bioinformatic workflows, like Parabricks, could greatly improve whole genome sequencing accessibility for clinical use by reduction of testing turnaround time

Speed-Aware Routing for UAV Ad-Hoc Networks

In this paper we examine mobile ad-hoc networks (MANET) composed by unmanned aerial vehicles (UAVs). Due to the high-mobility of the nodes, these networks are very dynamic and the existing routing protocols partly fail to provide a reliable communication. We present Predictive-OLSR an extension to the Optimized Link-State Routing (OLSR) protocol: it enables efficient routing in very dynamic conditions. The key idea is to exploit GPS information to aid the routing protocol. Predictive-OLSR weights the expected transmission count (ETX) metric, taking into account the relative speed between the nodes. We provide numerical results obtained by a MAC-layer emulator that integrates a flight simulator to reproduce realistic flight conditions. These numerical results show that Predictive-OLSR significantly outperforms OLSR and BABEL, providing a reliable communication even in very dynamic conditions.Comment: submitted to GlobeCom'13 Workshop - Wi-UA

Agarsenone, a Cadinane Sesquiterpenoid from Commiphora erythraea

Agarsenone (1), a new cadinane sesquiterpenoid, was isolated from the resin of Commiphora erythraea. The structures of 1 and its decomposition products agarsenolides (2a and 2b) and myrrhone (3) were established by extensive NMR spectroscopic analysis. The absolute configuration of 3 and the relative and absolute configurations of 1 were assigned by comparison of experimental and calculated optical rotatory dispersion and electronic circular dichroism spectr

Notch signaling sustains the expression of Mcl-1 and the activity of eIF4E to promote cell survival in CLL

In chronic lymphocytic leukemia (CLL), Notch1 and Notch2 signaling is constitutively activated and contributes to apoptosis resistance. We show that genetic inhibition of either Notch1 or Notch2, through small-interfering RNA, increases apoptosis of CLL cells and is associated with decreased levels of the anti-apoptotic protein Mcl-1. Thus, Notch signaling promotes CLL cell survival at least in part by sustaining Mcl-1 expression. In CLL cells, an enhanced Notch activation also contributes to the increase in Mcl-1 expression and cell survival induced by IL-4.Mcl-1 downregulation by Notch targeting is not due to reduced transcription or degradation by caspases, but in part, to increased degradation by the proteasome. Mcl-1 downregulation by Notch targeting is also accompanied by reduced phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), suggesting that this protein is another target of Notch signaling in CLL cells.Overall, we show that Notch signaling sustains CLL cell survival by promoting Mcl-1 expression and eIF4E activity, and given the oncogenic role of these factors, we underscore the therapeutic potential of Notch inhibition in CLL

Surgical options for atrial fibrillation treatment during concomitant cardiac procedures

Current guidelines recommend concomitant surgical ablation (SA) of atrial fibrillation (AF) in the context of mitral valve disease. A variety of energy sources have been tested for SA to perform effective transmural lesions reliably. To date, only radiofrequency and cryothermy energies are considered viable options. The gold standard for SA is the Cox -Maze ablation set, especially for non -paroxysmal AF (nPAF), with the aim of interrupting macro -reentrant drivers perpetuating AF, without hampering the sinus node activation of both atria, and to maintain the atrioventricular synchrony. Although the efficacy of SA in terms of early and late sinus rhythm restoration has been clearly demonstrated over the years, concomitant AF ablation is still underperformed in patients with AF undergoing cardiac surgery. From a surgical standpoint, concerns have been raised about whether a single (left) or double atriotomy would be justified in AF patients undergoing a "non-atriotomy" surgical procedure, such as aortic valve or revascularization surgery. Thus, an array of simplified lesion sets have been described in the last decade, which have unavoidably hampered procedural efficacy, somewhat jeopardizing the standardization process of ablation surgery. As a matter of fact, the term "Maze" has improperly become a generic term for SA. Surgical interventions that do not align with the principles of forming conduction -blocking lesions according to the Maze pattern, cannot be classified as Maze procedures. In this complex scenario, a tailored approach according to the different AF patterns has been proposed: for patients with concomitant nPAF, a biatrial Cox -Maze ablation is recommended. Conversely, it might be reasonable to limit lesions to the left atrium or the pulmonary veins in patients with paroxysmal AF (PAF) in some clinical scenarios. The aim of this review is to provide an overview of the current ablation strategies for patients with AF undergoing concomitant cardiac surgery

A Multi-Layered Study on Harmonic Oscillations in Mammalian Genomics and Proteomics

Cellular, organ, and whole animal physiology show temporal variation predominantly featuring 24-h (circadian) periodicity. Time-course mRNA gene expression profiling in mouse liver showed two subsets of genes oscillating at the second (12-h) and third (8-h) harmonic of the prime (24-h) frequency. The aim of our study was to identify specific genomic, proteomic, and functional properties of ultradian and circadian subsets. We found hallmarks of the three oscillating gene subsets, including different (i) functional annotation, (ii) proteomic and electrochemical features, and (iii) transcription factor binding motifs in upstream regions of 8-h and 12-h oscillating genes that seemingly allow the link of the ultradian gene sets to a known circadian network. Our multifaceted bioinformatics analysis of circadian and ultradian genes suggests that the different rhythmicity of gene expression impacts physiological outcomes and may be related to transcriptional, translational and post-translational dynamics, as well as to phylogenetic and evolutionary components