Computational Methods for Gene Expression and Genomic Sequence Analysis

Advances in technologies currently produce more and more cost-effective, high-throughput, and large-scale biological data. As a result, there is an urgent need for developing efficient computational methods for analyzing these massive data. In this dissertation, we introduce methods to address several important issues in gene expression and genomic sequence analysis, two of the most important areas in bioinformatics.Firstly, we introduce a novel approach to predicting patterns of gene response to multiple treatments in case of small sample size. Researchers are increasingly interested in experiments with many treatments such as chemicals compounds or drug doses. However, due to cost, many experiments do not have large enough samples, making it difficult for conventional methods to predict patterns of gene response. Here we introduce an approach which exploited dependencies of pairwise comparisons outcomes and resampling techniques to predict true patterns of gene response in case of insufficient samples. This approach deduced more and better functionally enriched gene clusters than conventional methods. Our approach is therefore useful for multiple-treatment studies which have small sample size or contain highly variantly expressed genes.Secondly, we introduce a novel method for aligning short reads, which are DNA fragments extracted across genomes of individuals, to reference genomes. Results from short read alignment can be used for many studies such as measuring gene expression or detecting genetic variants. Here we introduce a method which employed an iterated randomized algorithm based on FM-index, an efficient data structure for full-text indexing, to align reads to the reference. This method improved alignment performance across a wide range of read lengths and error rates compared to several popular methods, making it a good choice for community to perform short read alignment.Finally, we introduce a novel approach to detecting genetic variants such as SNPs (single nucleotide polymorphisms) or INDELs (insertions/deletions). This study has great significance in a wide range of areas, from bioinformatics and genetic research to medical field. For example, one can predict how genomic changes are related to phenotype in their organism of interest, or associate genetic changes to disease risk or medical treatment efficacy. Here we introduce a method which leveraged known genetic variants existing in well-established databases to improve accuracy of detecting variants. This method had higher accuracy than several state-of-the-art methods in many cases, especially for detecting INDELs. Our method therefore has potential to be useful in research and clinical applications which rely on identifying genetic variants accurately

Utilizing STEM-based practices to enhance mathematics teaching in Vietnam: Developing students' real-world problem solving and 21st century skills

In Vietnam, STEM-based teaching approaches have been recommended for schools since 2018 with the integration of multiple courses in schools. Teachers’ perspectives on integrated STEM education, and how to design a STEM lesson that supports students’ learning are critical for ensuring that an integrated STEM curriculum is to be implemented successfully. This paper aims to describe a study examining STEM education practices in teaching Mathematics, in particular “Trigonometry ratio of an acute angle” in Vietnam. This study utilized mixed methods approaches with three phases: the first stage employed a quantitative phase to examine Vietnamese teachers’ perspectives on STEM education. The second phase was an experiment on teaching while applying STEM education to design and organize a mathematics lesson, and the third, final phase, was to employ a qualitative study to explore the Vietnamese students’ experiences of STEM education connected with real-world problem-solving and 21st-century skills development. A total of 47 teachers and 85 students participated in this study and data was collected from multiple research tools such as questionnaires and semi-structured interviews. Findings showed Vietnamese teachers’ perspectives on the necessity and importance of applying STEM education practices; however, they reported facing numerous challenges. A lesson designed as a STEM education application and the students’ feedback in relation to real-world problems. Learning outcomes connected with 21st-century skills in this study were expected to provide further knowledge for further discussions and practices to enhance teaching and learning STEM and mathematics education in VietnamPeer Reviewe

Enhancing biogas production by anaerobic codigestion of water hyacinth and pig manure

The characteristics of anaerobic batch co-digestion of water hyacinth (WH) with pig manure (PM) under seven mixing ratio 100%WH; 80%WH : 20%PM; 60%WH : 40%PM; 50%WH : 50%PM; 40%WH : 60%PM; 20%WH : 80%PM and 100%PM were investigated, each treatment was conducted in five replications with daily loading rate at 1 gVS.L-1.day-1. During the anaerobic digestion process of 60 days, maximum biogas production occurred in two periods, the first stage from 12- 22 days and second stage from 30 - 35 days. The maximum daily biogas productions from each stage were 17.2 L.day-1 and 15.1 L.day-1, respectively. The cumulative biogas production varied between 60 L (100%PM) and 360 L (60%WH : 40%PM). The results showed that the biogas yields of co-digestion 40- 80%WH were higher from 34.6 to 56.1% in comparison with 100%PM and from 109 to 143% in comparison with 100%WH. When mixing with WH, treatments were received more methane and the methane contents were higher than 45% (v/v) that good for energy using purposes.Nghiên cứu được thực hiện nhằm khảo sát khả năng gia tăng lượng khí sinh học khi tiến hành đồng phân hủy yếm khí lục bình (WH) và phân heo (PM) ở các tỉ lệ phối trộn khác nhau gồm 100%WH; 80%WH : 20%PM; 60%WH : 40%PM; 50%WH : 50%PM; 40%WH : 60%PM; 20%WH : 80%PM và 100%PM. Các nghiệm thức được nạp lượng nguyên liệu là 1 gVS.L-1.ngày-1 và bố trí lặp lại 5 lần. Theo dõi quá trình phân hủy của các nghiệm thức trong 60 ngày ghi nhận có 2 khoảng thời gian lượng khí sản sinh nhiều nhất - giai đoạn 1 từ ngày 12 đến 22, giai đoạn 2 từ ngày 30 đến 35. Lượng khí sản sinh cao nhất tương ứng trong mỗi giai đoạn là 17.2 L.ngày-1 và 15.1 L.ngày-1. Lượng khí tích lũy trong suốt thời gian thí nghiệm ghi nhận thấp nhất ở nghiệm thức 100%PM đạt 60 L, và cao nhất ở nghiệm thức 60%WH : 40%PM đạt 360 L. Năng suất khí sinh ra của các nghiệm thức phối trộn lục bình từ 40 đến 80% cao hơn từ 34,6 đến 56,1% so với nghiệm thức 100%PM và cao hơn từ 109% đến 143% so với nghiệm thức 100%WH. Hàm lượng mê-tan sinh ra từ các nghiệm thức có phối trộn lục bình ổn định trong khoảng > 45% đảm bảo nhiệt lượng cho nhu cầu sử dụng năng lượng

Carbon Dioxide Utilisation -The Formate Route

UIDB/50006/2020 CEEC-Individual 2017 Program Contract.The relentless rise of atmospheric CO2 is causing large and unpredictable impacts on the Earth climate, due to the CO2 significant greenhouse effect, besides being responsible for the ocean acidification, with consequent huge impacts in our daily lives and in all forms of life. To stop spiral of destruction, we must actively reduce the CO2 emissions and develop new and more efficient “CO2 sinks”. We should be focused on the opportunities provided by exploiting this novel and huge carbon feedstock to produce de novo fuels and added-value compounds. The conversion of CO2 into formate offers key advantages for carbon recycling, and formate dehydrogenase (FDH) enzymes are at the centre of intense research, due to the “green” advantages the bioconversion can offer, namely substrate and product selectivity and specificity, in reactions run at ambient temperature and pressure and neutral pH. In this chapter, we describe the remarkable recent progress towards efficient and selective FDH-catalysed CO2 reduction to formate. We focus on the enzymes, discussing their structure and mechanism of action. Selected promising studies and successful proof of concepts of FDH-dependent CO2 reduction to formate and beyond are discussed, to highlight the power of FDHs and the challenges this CO2 bioconversion still faces.publishersversionpublishe

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Analysis of Microarray Data with Directed Graphs

This thesis studies various problems of analyzing microarray data with multiple treatments and multiple replicates using directed graphs. We start from a method that represents gene response as transitive directed acyclic graphs to extract meaningful information from microarray data (Phan et al., 2009). To extend this work, we simulate expressions of genes based on real data and make predictions about potential patterns of genes and their properties. From this, we predict whether such potential patterns are certain if given more replicates. Next, we used fold information which was not used in prior work to cluster genes share the same patterns and thus providing an additional layer of information. Finally, we created a web-based application to help other scientists try our method. The software assigns graphical patterns to genes and outputs images and textual data for further analyses

Analysis of Short-read Aligners using Genome Sequence Complexity

Next generation sequencing technologies have the capability to provide large numbers of short reads inexpensively and accurately. Researchers have proposed many different methods to align short reads to reference genomes. Nevertheless, long repeats, which are known to be abundant in eukaiyotic genomes, have caused considerable difficulty for genome assembly methods that rely on short-read alignment. Although a few researchers have studied sequence complexity of genomes in terms of repeats, none have quantitatively related such complexity to the difficulty of short read alignment and assembly. In this paper, we investigate several measures of genome sequence complexity with the goal of quantifying the difficulty of short read alignment Using genomic data from 17 different organisms and testing against 12 state-of-the-art short-read aligners, we found a very strong correlation between the performance of virtually all of these aligners and measures of genome sequence complexity. Further, we show how these measures might be used to analyze and predict the performance of aligners, and more importantly, select the best aligners for specific genomes

Active Learning: The Almost Silver Bullet

Despite its clear benefits, Active Learning (AL) has gone widely unused in favor of traditional teaching models, due to AL\u27s higher costs. With the increased prevalence of software based teaching aids, many of these barriers have been removed and new Active Learning strategies can be more easily implemented. We show that AL can be utilized in the classroom to improve work efficiency, better use TAs, and achieve positive gains in student performance and understanding using integrated lab work

Early outcomes of total hip arthroplasty using point-of-care manufactured patient-specific instruments: a single university hospital’s initial experience

Abstract Background The use of 3D-printed Patient-Specific Instruments (PSI) has been investigated to enhance the postoperative functional results in total hip arthroplasty (THA) and has been recognized as an innovative approach for the optimal alignment of hip implant components. Point-of-care production is gradually becoming the norm for PSI manufacturing. The purpose of this article is to assess the accuracy and safety of PSI for total hip arthroplasty performed at the point-of-care in Vietnam. Methods 34 THA cases were assessed in this prospective study. A template for the size and orientation of the implant and the design of the PSI was generated using data from preoperative 3D computed tomography (CT) scanning of the lower limb. The principal surgeon determined the implants’ position and PSI design directly using the software. The PSI is then produced using a 3D-compatible resin printer in our manufacturing hospital. The PSI, consisting of an acetabulum and a femoral component placed press-fit on the bony surface, guided surgeons to precisely ream the acetabulum and cut the femoral neck according to the pre-planned plane. Postoperative CT scanning was obtained and superimposed onto the 3D model of the implant to evaluate the accuracy of the procedure by comparing the orientation values of the cup and the alignment of the stem between the planned and the actual results. Intra- and postoperative clinical parameters of surgery, including surgical time, intra-operative blood loss, complications, and the first ambulation, were also recorded to evaluate the safety of the surgery. Results The preparation for PSI required an average of 3 days. 94% of cup size and 91% of stem size were correctly selected. The mean values of postoperative inclination and anteversion were 44.2° ± 4.1° and 19.2° ± 5.6°, respectively. 64.7% of cases deviated from planned within the ± 50 range and 94.1% within the ± 10° range. There was no significant statistical difference between the planned and the achieved values of stem anteversion, osteotomy height, and leg length discrepancy (p > 0.05). The average surgical time was 82.5° ± 10.8 min, and the intraoperative blood loss was estimated at 317.7° ± 57.6 ml. 64.7% of patients could walk on the day of surgery. There were no complications reported. Conclusions The point-of-care manufactured PSI is a useful solution for improving the accuracy of total hip arthroplasty surgery, especially in restoring implant orientation and reducing leg length discrepancy. However, long-term clinical follow-up evaluation is needed to confirm the efficacy and safety of this approach