Wang Y.,Shanghai JiaoTong University |
Wang Y.,Beijing Jiaotong University |
Wang Y.,Key Laboratory of Embryo Molecular Biology |
Wang Y.,Shanghai Laboratory of Embryo and Reproduction Engineering |
And 21 more authors.
European Journal of Pediatrics | Year: 2014
It has been hypothesized that dysregulation of brain-expressed genes is the major predisposing underlying mechanism for autism. This dysregulation may be mediated by differential methylation of CpG sites within gene promoters, which could be candidate biomarkers and used for early clinical screening of autism. A total of 131 pairs of age- and sex-matched autistic and control subjects were recruited in this study. Peripheral blood cells were analyzed. The first five pairs were randomly applied to array-based genome-wide methylation studies. A neuron-specific gene, ENO2, was found to be hypermethylated in the autistic samples. This difference was validated by bisulfite sequencing PCR (BSP). The differential expression of ENO2 gene was further analyzed with RT-qPCR and ELISA. The hypermethylation of ENO2 within the promoter region was confirmed by BSP to be present in 14.5 % (19/131) of the total of the autistic samples. The mean ENO2 RNA level in these 19 autistic samples was reduced by about 70 % relative to that in controls. The average level of ENO2 protein expression in the 19 autistic samples (15.18±3.51 μg/l) was about half of that in the controls (33.86±8.16 μg/l). Conclusion: These findings suggest that reduced ENO2 expression may be a biomarker for a subset of autistic children. © 2014 The Author(s).
Li B.-Q.,CAS Shanghai Institutes for Biological Sciences |
Li B.-Q.,Shanghai Center for Bioinformation Technology |
Cai Y.-D.,Shanghai University |
Feng K.-Y.,CAS Beijing Institute of Genomics |
And 3 more authors.
PLoS ONE | Year: 2012
Proteinases play critical roles in both intra and extracellular processes by binding and cleaving their protein substrates. The cleavage can either be non-specific as part of degradation during protein catabolism or highly specific as part of proteolytic cascades and signal transduction events. Identification of these targets is extremely challenging. Current computational approaches for predicting cleavage sites are very limited since they mainly represent the amino acid sequences as patterns or frequency matrices. In this work, we developed a novel predictor based on Random Forest algorithm (RF) using maximum relevance minimum redundancy (mRMR) method followed by incremental feature selection (IFS). The features of physicochemical/biochemical properties, sequence conservation, residual disorder, amino acid occurrence frequency, secondary structure and solvent accessibility were utilized to represent the peptides concerned. Here, we compared existing prediction tools which are available for predicting possible cleavage sites in candidate substrates with ours. It is shown that our method makes much more reliable predictions in terms of the overall prediction accuracy. In addition, this predictor allows the use of a wide range of proteinases. © 2012 Li et al.
He X.,Beijing Jiaotong University |
He X.,Key Laboratory of Embryo Molecular Biology |
He X.,Shanghai Laboratory of Embryo and Reproduction Engineering |
Xie F.,Shanghai JiaoTong University |
And 3 more authors.
Genetic Testing and Molecular Biomarkers | Year: 2012
Achondroplasia (ACH) is a genetic disorder with autosomal dominant inheritance and is the cause of one of the most common forms of short limb dwarfism in humans. Mutations of special sites in the fibroblast growth factor receptor-3 gene (FGFR3) are reported as a cause of ACH, and almost 98% of cases are caused by mutations in nucleotide 1138 (Gly380Arg), with 97% involving a c.1138G>A mutation and 1% involving a c.1138G>C mutation. Therefore, the development of a simple, reliable, and rapid approach for molecular detection of nucleotide 1138 mutations is of great significance for prevention and early diagnosis of.ACH. High-resolution melting (HRM) is a new, rapid, and inexpensive molecular detection method that has been generally applied to mutation scanning. In this study, 12 cases of ACH, including 10 sporadic cases and 2 cases in a pedigree, were detected simultaneously using HRM analysis and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Eleven cases were identified as carrying the c.1138 G>A heterozygous mutation, and one case was identified as carrying the c.1138 G>C heterozygous mutation. Compared with RFLP-PCR, HRM analysis provided a more rapid, simpler, and less expensive approach for detecting the most common FGFR3 mutations carried by patients with ACH. © Copyright 2012, Mary Ann Liebert, Inc.
Moussa M.,Shanghai JiaoTong University |
Moussa M.,The Key Laboratory of Embryo Molecular Biology |
Moussa M.,Shanghai Laboratory of Embryo and Reproduction Engineering |
Moussa M.,Shanghai Tao Tao Transgenic Corporation |
And 10 more authors.
Science China Life Sciences | Year: 2014
Cryopreservation techniques for mammalian oocytes and embryos have rapidly progressed during the past two decades, emphasizing their importance in various assisted reproductive technologies. Pregnancies and live births resulting from cryopreserved oocytes and embryos of several species including humans have provided proof of principle and led to the adoption of cryopreservation as an integral part of clinical in vitro fertilization. Considerable progress has been achieved in the development and application of the cryopreservation of mammalian oocytes and embryos, including preservation of the reproductive potential of patients who may become infertile, establishment of cryopreserved oocyte banks, and transport of oocytes and embryos internationally. However, the success rates are still far lower than those obtained with fresh oocytes and embryos, and there are still obstacles that need to be overcome. In this review, we address the major obstacles in the development of effective cryopreservation techniques. Such knowledge may help to eliminate these hurdles by revealing which aspects need improvement. Furthermore, this information may encourage further research by cryobiologists and increase the practical use of cryopreservation as a major part of assisted reproductive technologies for both humans and animal species. © 2014 The Author(s).
Yan J.-B.,Beijing Jiaotong University |
Yan J.-B.,Key Laboratory of Embryo Molecular Biology |
Yan J.-B.,Shanghai Laboratory of Embryo and Reproduction Engineering |
Xu H.-P.,Shanghai Childrens Hospital |
And 14 more authors.
Journal of Molecular Diagnostics | Year: 2010
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked inherited disease, is one of the most common enzymopathies and affects over 400 million people worldwide. In China at least 21 distinct point mutations have been identified so far. In this study high-resolution melting (HRM) analysis was used to screen for G6PD mutations in 260 unrelated Han Chinese individuals, and the rapidity and reliability of this method was investigated. The mutants were readily differentiated by using HRM analysis, which produced distinct melting curves for each tested mutation. Interestingly, G1388A and G1376T, the two most common variants accounting for 50% to 60% of G6PD deficiency mutations in the Chinese population, could be differentiated in a single reaction. Further, two G6PD mutations not previously reported in the Chinese population were identified in this study. One of these mutations, designated "G6PD Jiangxi G1340T," involved a G1340T substitution in exon 11, predicting a Gly447Val change in the protein. The other mutation involved a C406T substitution in exon 5. The frequencies of the common polymorphism site C1311T/IVS (intervening sequence) XI t93c between patients with G6PD and healthy volunteers were not significantly different. Thus, HRM analysis will be a useful alternative for screening G6PD mutations. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology.
Kallberg M.,University of Illinois at Chicago |
Bhardwaj N.,University of Illinois at Chicago |
Bhardwaj N.,Yale University |
Langlois R.,University of Illinois at Chicago |
And 5 more authors.
Bioinformatics | Year: 2012
Motivation: Peripheral membrane-targeting domain (MTD) families, such as C1-, C2- and PH domains, play a key role in signal transduction and membrane trafficking by dynamically translocating their parent proteins to specific plasma membranes when changes in lipid composition occur. It is, however, difficult to determine the subset of domains within families displaying this property, as sequence motifs signifying the membrane binding properties are not well defined. For this reason, procedures based on sequence similarity alone are often insufficient in computational identification of MTDs within families (yielding less than 65% accuracy even with a sequence identity of 70%). Results: We present a machine learning protocol for determining membrane-targeting properties achieving 85-90% accuracy in separating binding and non-binding domains within families. Our model is based on features from both sequence and structure, thereby incorporation statistics obtained from the entire domain family and domain-specific physical quantities such as surface electrostatics. In addition, by using the enriched rules in alternating decision tree classifiers, we are able to determine the meaning of the assigned function labels in terms of biological mechanisms. Conclusions: The high accuracy of the learned models and good agreement between the rules discovered using the ADtree classifier and mechanisms reported in the literature reflect the value of machine learning protocols in both prediction and biological knowledge discovery. Our protocol can thus potentially be used as a general function annotation and knowledge mining tool for other protein domains. © The Author(s) 2012. Published by Oxford University Press.
Genchev G.Z.,University of Illinois at Chicago |
Kobayashi T.,University of Illinois at Chicago |
Lu H.,University of Illinois at Chicago |
Lu H.,Childrens Hospital of Shanghai |
And 2 more authors.
PLoS ONE | Year: 2013
The interaction between calcium and the regulatory site(s) of striated muscle regulatory protein troponin switches on and off muscle contraction. In skeletal troponin binding of calcium to sites I and II of the TnC subunit results in a set of structural changes in the troponin complex, displaces tropomyosin along the actin filament and allows myosin-actin interaction to produce mechanical force. In this study, we used molecular dynamics simulations to characterize the calcium dependent dynamics of the fast skeletal troponin molecule and its TnC subunit in the calcium saturated and depleted states. We focused on the N-lobe and on describing the atomic level events that take place subsequent to removal of the calcium ion from the regulatory sites I and II. A main structural event - a closure of the A/B helix hydrophobic pocket results from the integrated effect of the following conformational changes: the breakage of H-bond interactions between the backbone nitrogen atoms of the residues at positions 2, 9 and sidechain oxygen atoms of the residue at position 12 (N2-OE12/N9-OE12) in sites I and II; expansion of sites I and II and increased site II N-terminal end-segment flexibility; strengthening of the β-sheet scaffold; and the subsequent re-packing of the N-lobe hydrophobic residues. Additionally, the calcium release allows the N-lobe to rotate relative to the rest of the Tn molecule. Based on the findings presented herein we propose a novel model of skeletal thin filament regulation. © 2013 Genchev et al.