Jeerayut Chaijaruwanich

BACKGROUND: Dengue virus infection causes an array of symptoms ranging from dengue fever (DF) to dengue hemorrhagic fever (DHF). The pathophysiological processes behind these 2 clinical manifestations are unclear. METHOD: In the present study, genomewide transcriptomes of peripheral blood mononuclear cells (PBMCs) collected from children with acute-phase DF (i.e., DF PBMCs) or acute-phase DHF (i.e., DHF PBMCs) were compared using microarray analysis. Results of genome screening were validated at the genomic and proteomics levels. RESULTS: DHF had stronger influences on the gene expression profile than did DF. Of the affected genes, metabolic gene expression was influenced the most. For the immune response category, 17 genes were more strongly up-regulated in DF PBMCs than in DHF PBMCs. Eight of the these 17 genes were categorized as belonging to the interferon (IFN) system. The up-regulation of IFN-related genes was accompanied by strong expression of CD59, a complement inhibitor. DHF PBMCs expressed genes involved in T and B cell activation, cytokine production, complement activation, and T cell apoptosis more strongly than did DF PBMCs. CONCLUSION: We hypothesize that, during DF, genes in the IFN system and complement inhibitor play a role in lowering virus production and reducing tissue damage. In patients with DHF, the dysfunction of immune cells, complement, and cytokines increases viral load and tissue damage.

Existing methods for predicting protein crystallization obtain high accuracy using various types of complemented features and complex ensemble classifiers, such as support vector machine (SVM) and Random Forest classifiers. It is desirable to develop a simple and easily interpretable prediction method with informative sequence features to provide insights into protein crystallization. This study proposes an ensemble method, SCMCRYS, to predict protein crystallization, for which each classifier is built by using a scoring card method (SCM) with estimating propensity scores of p-collocated amino acid (AA) pairs (p=0 for a dipeptide). The SCM classifier determines the crystallization of a sequence according to a weighted-sum score. The weights are the composition of the p-collocated AA pairs, and the propensity scores of these AA pairs are estimated using a statistic with optimization approach. SCMCRYS predicts the crystallization using a simple voting method from a number of SCM classifiers. The experimental results show that the single SCM classifier utilizing dipeptide composition with accuracy of 73.90% is comparable to the best previously-developed SVM-based classifier, SVM_POLY (74.6%), and our proposed SVM-based classifier utilizing the same dipeptide composition (77.55%). The SCMCRYS method with accuracy of 76.1% is comparable to the state-of-the-art ensemble methods PPCpred (76.8%) and RFCRYS (80.0%), which used the SVM and Random Forest classifiers, respectively. This study also investigates mutagenesis analysis based on SCM and the result reveals the hypothesis that the mutagenesis of surface residues Ala and Cys has large and small probabilities of enhancing protein crystallizability considering the estimated scores of crystallizability and solubility, melting point, molecular weight and conformational entropy of amino acids in a generalized condition. The propensity scores of amino acids and dipeptides for estimating the protein crystallizability can aid biologists in designing mutation of surface residues to enhance protein crystallizability. The source code of SCMCRYS is available at http://iclab.life.nctu.edu.tw/SCMCRYS/.

BACKGROUND: Starch serves as a temporal storage of carbohydrates in plant leaves during day/night cycles. To study transcriptional regulatory modules of this dynamic metabolic process, we conducted gene regulation network analysis based on small-sample inference of graphical Gaussian model (GGM). RESULTS: Time-series significant analysis was applied for Arabidopsis leaf transcriptome data to obtain a set of genes that are highly regulated under a diurnal cycle. A total of 1,480 diurnally regulated genes included 21 starch metabolic enzymes, 6 clock-associated genes, and 106 transcription factors (TF). A starch-clock-TF gene regulation network comprising 117 nodes and 266 edges was constructed by GGM from these 133 significant genes that are potentially related to the diurnal control of starch metabolism. From this network, we found that β-amylase 3 (b-amy3: At4g17090), which participates in starch degradation in chloroplast, is the most frequently connected gene (a hub gene). The robustness of gene-to-gene regulatory network was further analyzed by TF binding site prediction and by evaluating global co-expression of TFs and target starch metabolic enzymes. As a result, two TFs, indeterminate domain 5 (AtIDD5: At2g02070) and constans-like (COL: At2g21320), were identified as positive regulators of starch synthase 4 (SS4: At4g18240). The inference model of AtIDD5-dependent positive regulation of SS4 gene expression was experimentally supported by decreased SS4 mRNA accumulation in Atidd5 mutant plants during the light period of both short and long day conditions. COL was also shown to positively control SS4 mRNA accumulation. Furthermore, the knockout of AtIDD5 and COL led to deformation of chloroplast and its contained starch granules. This deformity also affected the number of starch granules per chloroplast, which increased significantly in both knockout mutant lines. CONCLUSIONS: In this study, we utilized a systematic approach of microarray analysis to discover the transcriptional regulatory network of starch metabolism in Arabidopsis leaves. With this inference method, the starch regulatory network of Arabidopsis was found to be strongly associated with clock genes and TFs, of which AtIDD5 and COL were evidenced to control SS4 gene expression and starch granule formation in chloroplasts.

Arthrospira platensis is a cyanobacterium that is extensively cultivated outdoors on a large commercial scale for consumption as a food for humans and animals. It can be grown in monoculture under highly alkaline conditions, making it attractive for industrial production. Here we describe the complete genome sequence of A. platensis C1 strain and its annotation. The A. platensis C1 genome contains 6,089,210 bp including 6,108 protein-coding genes and 45 RNA genes, and no plasmids. The genome information has been used for further comparative analysis, particularly of metabolic pathways, photosynthetic efficiency and barriers to gene transfer.

The most common cause of long-term disability and death in young adults is a traumatic brain injury. The decision for surgical intervention for craniotomy is dependent on the injury type and the patient's neurologic exam. The potential subtypes of intracranial hemorrhage that may necessitate surgical intervention include subdural hemorrhage, epidural hemorrhage, and intraparenchymal hemorrhage. We proposed a novel automatic method for segmenting the hemorrhage subtypes on a CT scan by integrated CT scan with bone window as input of a deep learning model. Brain CT scans were collected from adult patients and annotated regions of subdural hemorrhage, epidural hemorrhage, and intraparenchymal hemorrhage by neuroradiologists. Their raw DICOM images were preprocessed by two different window settings i.e., subdural and bone windows. The collected CT scans were divided into two datasets namely training and test datasets. A deep-learning model was modified to segment regions of each hemorrhage subtype. The model is a three-dimensional convolutional neural network including four parallel pathways that process the input at different resolutions. It was trained by a training dataset. After the segmentation result was produced by the deep-learning model, it was then improved in the post-processing step. The size of the segmented lesion was considered, and a region-growing algorithm was applied. We evaluated the performance of the proposed method on the test dataset. The method reached the median Dice similarity coefficients higher than 0.37 for each hemorrhage subtype. The proposed method demonstrates higher Dice similarity coefficients and improved segmentation performance compared to previously published literature.