Joint Haplotype Assembly and Genotype Calling via Sequential Monte Carlo Algorithm

Genetic variations predispose individuals to hereditary diseases, play important role in the development of complex diseases, and impact drug metabolism. The full information about the DNA variations in the genome of an individual is given by haplotypes, the ordered lists of single nucleotide polymorphisms (SNPs) located on chromosomes. Affordable high-throughput DNA sequencing technologies enable routine acquisition of data needed for the assembly of single individual haplotypes. However, state-of-the-art high-throughput sequencing platforms generate data that is erroneous, which induces uncertainty in the SNP and genotype calling procedures and, ultimately, adversely affect the accuracy of haplotyping. When inferring haplotype phase information, the vast majority of the existing techniques for haplotype assembly assume that the genotype information is correct. This motivates the development of methods capable of joint genotype calling and haplotype assembly. Results: We present a haplotype assembly algorithm, ParticleHap, that relies on a probabilistic description of the sequencing data to jointly infer genotypes and assemble the most likely haplotypes. Our method employs a deterministic sequential Monte Carlo algorithm that associates single nucleotide polymorphisms with haplotypes by exhaustively exploring all possible extensions of the partial haplotypes. The algorithm relies on genotype likelihoods rather than on often erroneously called genotypes, thus ensuring a more accurate assembly of the haplotypes. Results on both the 1000 Genomes Project experimental data as well as simulation studies demonstrate that the proposed approach enables highly accurate solutions to the haplotype assembly problem while being computationally efficient and scalable, generally outperforming existing methods in terms of both accuracy and speed. Conclusions: The developed probabilistic framework and sequential Monte Carlo algorithm enable joint haplotype assembly and genotyping in a computationally efficient manner. Our results demonstrate fast and highly accurate haplotype assembly aided by the re-examination of erroneously called genotypes.National Science Foundation CCF-1320273Electrical and Computer Engineerin

Computational methods for understanding genetic variations from next generation sequencing data

Studies of human genetic variation reveal critical information about genetic and complex diseases such as cancer, diabetes and heart disease, ultimately leading towards improvements in health and quality of life. Moreover, understanding genetic variations in viral population is of utmost importance to virologists and helps in search for vaccines. Next-generation sequencing technology is capable of acquiring massive amounts of data that can provide insight into the structure of diverse sets of genomic sequences. However, reconstructing heterogeneous sequences is computationally challenging due to the large dimension of the problem and limitations of the sequencing technology.This dissertation is focused on algorithms and analysis for two problems in which we seek to characterize genetic variations: (1) haplotype reconstruction for a single individual, so-called single individual haplotyping (SIH) or haplotype assembly problem, and (2) reconstruction of viral population, the so-called quasispecies reconstruction (QSR) problem. For the SIH problem, we have developed a method that relies on a probabilistic model of the data and employs the sequential Monte Carlo (SMC) algorithm to jointly determine type of variation (i.e., perform genotype calling) and assemble haplotypes. For the QSR problem, we have developed two algorithms. The first algorithm combines agglomerative hierarchical clustering and Bayesian inference to reconstruct quasispecies characterized by low diversity. The second algorithm utilizes tensor factorization framework with successive data removal to reconstruct quasispecies characterized by highly uneven frequencies of its components. Both algorithms outperform existing methods in both benchmarking tests and real data.Electrical and Computer Engineerin

Student Academic Performance Outcomes of a Classroom Physical Activity Intervention: A Pilot Study

A Physical activity is beneficial to children’s health, yet academic pressures limit opportunities forstudents throughout the school day. The purpose of this study was to determine the effect of aclassroom PA intervention on student academic performance outcomes. Intervention participants(n=15) received daily PA breaks. Reading and mathematics fluency, PA, grades, and standardized testscores were collected. Effects of the intervention were examined using mixed-design ANOVAs.Intervention students had significantly higher reading fluency and mathematics scores postinterventionand higher means for standardized reading and mathematics scores as well as grades.Short bouts of PA are important for improving CBM math and reading fluency scores. Classroomteachers should be encouraged to devote time during academic learning to incorporate PA

LOCAT (low-dose computed tomography for appendicitis trial) comparing clinical outcomes following low- vs standard-dose computed tomography as the first-line imaging test in adolescents and young adults with suspected acute appendicitis: study protocol for a randomized controlled trial

Trial registration : ClinicalTrials.gov NCT01925014Background : Computed tomography is widely used to diagnose acute appendicitis. Many adolescents and young adults are exposed to the associated radiation. A recent single-institution trial has reported promising results for low-dose computed tomography; however, this technique has not yet been widely adopted. LOCAT (low-dose computed tomography for appendicitis trial), a multi-institution randomized controlled non-inferiority trial, aims to compare low-dose computed tomography and standard-dose computed tomography as the first-line imaging tests for adolescents and young adults, and therefore to test the generalizability of the previous single-institution trial results. Methods/Design : Participants with suspected appendicitis are randomly assigned to either the low-dose group (with a typical effective dose of 2 mSv) or the standard-dose group (as used in normal practice at each participating site, typically 8 mSv). The primary end point is the negative appendectomy rate (the percentage of the number of uninflamed appendices that were removed among all non-incidental appendectomies), which is a consequence of false-positive diagnoses, with a non-inferiority margin of 4.5 percentage points. The key secondary end point is the appendiceal perforation rate, which is a consequence of delayed (or false-negative) diagnoses. Participant recruitment will be continued until the number of non-incidental appendectomies for each group exceeds 444. The total number of expected participants approximates 3,000, including those not undergoing appendectomy. Discussion : In addition to the study protocol, we elaborate on several challenging or potentially debatable components of the study design, including the broad eligibility criteria, choice of the primary end point, potential effect of using advanced imaging techniques on study results, determining and adjusting the radiation doses, ambiguities in reference standards, rationale for the non-inferiority margin, use of the intention-to-treat approach and difficulties in defining adverse events.LOCAT is funded by the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI13C00040200), the Medical Research Collaborating Center, Seoul National University Bundang Hospital (02-2013-091) and Dasol Life Science Inc (06-2013-107Peer Reviewe

Global analyses of mRNA translational control during early Drosophila embryogenesis

The polysomal profiles of over 15,000 transcripts during the first ten hours after egg laying have been determined

The Use of Bicycle Desks to Increase Physical Activity in Two Special Education Classrooms

BACKGROUND Although the literature has predominantly focused on elementary youth, preliminary findings indicate that attentional benefits may arise from adolescent physical activity as well. Limited research has examined the impact of classroom-based physical activity for secondary students, and no research to date has explored bicycle workstations as a means to improve physical activity within the special education classroom. PARTICIPANTS AND PROCEDURE Two special education resource classrooms within a high school took part in the research study. Students were given the option of riding on the bike or sitting on chairs in each classroom. Heart rate, calories, miles, time, and on-task behavior data were collected. In addition, student acceptability of bikes was explored. RESULTS The results indicated that the overall mean heart rate during bike riding was significantly higher than the overall mean heart rate when seated on a traditional chair. Also a significant main effect was found for time on calories expended while riding. No significant results were found for miles or on-task behavior. CONCLUSIONS Overall, students enjoyed the use of bicycles during class, found the bicycle workstations to be beneficial to their learning, and appeared to note as many benefits as limitations with the bicycle workstations. Limitations and future directions are discussed

Epidemiology of sepsis in Korea: a population-based study of incidence, mortality, cost and risk factors for death in sepsis

Objective To investigate the epidemiology of sepsis in Korea and identify risk factors for death in sepsis. Methods We conducted a longitudinal, population-based epidemiological study of sepsis in Korea from 2005 to 2012 using the National Health Insurance Service-National Sample Cohort, a population-based cohort representing 2.2% of the Korean population. The primary objective was to assess the incidence, mortality and cost of sepsis. The secondary objective was to identify the risk factors for death in sepsis. Claim records of admitted adult patients (aged ≥15 years) were analyzed. Sepsis was defined as 1) bacterial or fungal infection or the conditions they often complicate, 2) prescription of intravenous antibiotics, and 3) presence of any organ dysfunction. Comorbidities were defined using the Charlson/Deyo method. Risk factors for 6-month mortality were assessed using multivariable logistic regression. Results A total of 22,882 cases were identified. Both incidence and 6-month mortality increased from 265.7 (95% confidence interval [CI], 254.7 to 277.1) to 453.1 (95% CI, 439.0 to 467.5) per 100,000 person-years (P-trend <0.001) and from 26.5% (95% CI, 24.4% to 28.8%) to 30.1% (95% CI, 28.4% to 31.9%), respectively. After standardization, the increasing trend of incidence was slower but still significant (P-trend <0.001), while that for mortality was not (P-trend 0.883). The average cost increased by 75.5% (P-trend <0.001). Multivariable logistic regression identified various risk factors for mortality. Conclusion The burden of sepsis in Korea was high and is expected to increase considering the aging population. Proactive measures to curtail this increase should be sought and implemented