Clotho: addressing the scalability of forward time population genetic simulation.

BACKGROUND: Forward Time Population Genetic Simulations offer a flexible framework for modeling the various evolutionary processes occurring in nature. Often this model expressibility is countered by an increased memory usage or computational overhead. With the complexity of simulation scenarios continuing to increase, addressing the scalability of the underlying simulation framework is a growing consideration. RESULTS: We propose a general method for representing in silico genetic sequences using implicit data structures. We provide a generalized implementation as a C++ template library called Clotho. We compare the performance and scalability of our approach with those taken in other simulation frameworks, namely: FWDPP and simuPOP. CONCLUSIONS: We show that this technique offers a 4x reduction in memory utilization. Additionally, with larger scale simulation scenarios we are able to offer a speedup of 6x-46x.

A comparison study of succinct data structures for use in GWAS.

BACKGROUND: In recent years genetic data analysis has seen a rapid increase in the scale of data to be analyzed. Schadt et al (NRG 11:647-657, 2010) offered that with data sets approaching the petabyte scale, data related challenges such as formatting, management, and transfer are increasingly important topics which need to be addressed. The use of succinct data structures is one method of reducing physical size of a data set without the use of expensive compression techniques. In this work, we consider the use of 2- and 3-bit encoding schemes for genotype data. We compare the computational performance of allele or genotype counting algorithms utilizing genotype data encoded in both schemes. RESULTS: We perform a comparison of 2- and 3-bit genotype encoding schemes for use in genotype counting algorithms. We find that there is a 20% overhead when building simple frequency tables from 2-bit encoded genotypes. However, building pairwise count tables for genome-wide epistasis is 1.0% more efficient. CONCLUSIONS: In this work, we were concerned with comparing the performance benefits and disadvantages of using more densely packed genotype data representations in Genome Wide Associations Studies (GWAS). We implemented a 2-bit encoding for genotype data, and compared it against a more commonly used 3-bit encoding scheme. We also developed a C++ library, libgwaspp, which offers these data structures, and implementations of several common GWAS algorithms. In general, the 2-bit encoding consumes less memory, and is slightly more efficient in some algorithms than the 3-bit encoding.

Development and evaluation of hardware for Point-of-Care assessment of upper-limb motor performance.

This paper presents prototypes of a hardware interface that is directed towards possible integration with a Point-of-Care Testing Environment for Neurological Assessment (POCTENA). While the complete system is intended to assist with diagnosis of mild Traumatic Brain Injury (TBI), the focus of this paper is to present designs of necessary hardware that can be used to assess upper-limb motor performance in a point-of-care setting. The hardware interface is expected to facilitate execution of several visuomotor tasks in an attempt to reliably quantify motor deficits. System usability results are shown to corroborate future directions of the POCTENA system.

Design and usability of a medical computing system for diagnosis of mild traumatic brain injury.

In this paper, we present a prototype design of POCTENA (Point-Of-Care Testing Environment for Neurological Assessment), a medical computing system that will be used to assist with diagnosis of mild traumatic brain injury. The design includes an initial set of neurological tests that are built into the system. Component-based usability testing was conducted to examine the effectiveness of the user interface. Results from usability testing are then used to suggest possible system design revisions.

Device for quantification of bilirubin in cerebral spinal fluid.

In North America, an estimated 30,000 patients annually experience an aneurysmal subarachnoid hemorrhage (SAH). In approximately five percent of these patients, the hemorrhage is not visible on computerized tomography scans due to the inability to image blood at time intervals greater than 12 h post symptom onset. For these patients (many of which have experienced a sentinel hemorrhage that is a precursor to a more significant rupture), a method is needed for accurately analyzing cerebral spinal fluid (CSF) for evidence of SAH. Further, it is necessary to differentiate blood associated with the SAH from blood associated with the spinal tap procedure. This letter presents a point-of-care device that is capable of performing such an analysis. The stand-alone prototype device uses commercially available embedded system components to implement a point-of-care device that is capable of collecting and analyzing optical absorbance spectra. A mathematical model for the hemorrhagic CSF sample is then developed by using a partial-least-squares-regression-based regression methodology that is able to differentiate between SAH and blood associated with the spinal tap. This differentiation is achieved by quantifying bilirubin (associated with the breakdown of old blood) in the CSF. Initial testing on the prototype device suggests that the device is able to quantify bilirubin in the presence of hemoglobin over concentrations ranges that are clinically relevant to the patient population of interest.

Development of a point-of-care device for the quantification of bilirubin in cerebral spinal fluid.

In North America, an estimated 30,000 patients annually experience an aneurysmal subarachnoid hemorrhage (SAH). In approximately five percent of these patients, the hemorrhage is not visible on computerized tomography scans due to the inability to image blood at time intervals greater than 12 hours post symptom onset. For these patients (many of which have experience a sentinel hemorrhage that is a precursor to a more significant rupture) a method is needed for accurately analyzing cerebral spinal fluid (CSF) for evidence of SAH. Further, it is necessary to differentiate blood associated with the SAH from blood associated with the spinal tap procedure. This paper presents the development of a point-of-care device that is capable of performing such an analysis. The stand alone prototype device uses commercially available embedded system components to implement a hardware platform that is capable of collecting and analyzing optical absorbance spectra. A mathematical model for the hemorrhagic CSF sample is then developed using a PLSR based regression methodology that is able to differentiate between SAH and blood associated with the spinal tap. This differentiations in achieved by quantifying bilirubin (associated with the breakdown of old blood) in the CSF. Initial testing on the prototype device suggests that the device is able to quantify bilirubin in the presence of hemoglobin over concentrations ranges that are clinically relevant to the patient population of interest.

Virtual preoperative measurement and surgical manipulation of sagittal spinal alignment using a novel research and educational software program.

Understanding regional as well as global spinal alignment is increasingly recognized as important for the spine surgeon. A novel software program for virtual preoperative measurement and surgical manipulation of sagittal spinal alignment was developed to provide a research and educational tool for spine surgeons. This first-generation software program provides tools to measure sagittal spinal alignment from the occiput to the pelvis, and to allow for virtual surgical manipulation of sagittal spinal alignment. The software was developed in conjunction with Clifton Labs, Inc. Photographs and radiographs were imported into the software program, and a 2D virtual spine was constructed from the images. The software then measured regional and global sagittal spinal alignment from the virtual spine construct, showing the user how to perform the measurements. After measuring alignment, the program allowed for virtual surgical manipulation, simulating surgical procedures such as interbody fusion, facet osteotomy, pedicle subtraction osteotomy, and reduction of spondylolisthesis, as well as allowing for rotation of the pelvis on the hip axis. Following virtual manipulation, the program remeasured regional and global sagittal spinal alignment. Computer software can be used to measure and manipulate sagittal spinal alignment virtually, providing a new research and educational tool. In the future, more comprehensive programs may allow for measurement and interaction in the coronal, axial, and sagittal planes.