基于测序软件进行生物信息学中数据分析

概述了生物信息学中的一些研究方向及分析方法,介绍了用于大规模DNA测序的分析软件系统——Phred/Phrap/Consed。通过利用Phred/Phrap/Consed等各种分析软件,时基因组学、蛋白质组学和基因芯片研究中巨量原始实验数据进行分析、处理,使之成为具有明确生物学意义的生物信息。     

基于PC/Linux的核酸序列分析系统的构建及其应用

基于PC机和Linux操作系统, 利用Phred/Phrap/Consed软件和Blast软件, 构建了核酸序列大规模自动分析系统. 该套系统可自动完成从测序峰图向核酸序列的转化、载体序列去除、序列自动拼接、重复序列鉴定以及序列的相似性分析, 可加速对大规模测序数据的分析和利用.     

基于GPL软件的小型生物实验室计算服务解决方案

针对小型实验室特点和实际需要,提出并实现一个以服务器-客户机模式,涵盖web服务,生物序列分析,生物芯片数据分析,实验数据统计处理,文献服务等计算机辅助的通用解决方案。该解决方案已经应用在批量ESTs电子注释和寄生虫病分子诊断的靶序列筛选上。可作为小型实验室生物信息学基础设施部署。     

基于PC/Linux的致敏性评估网站的构建及其应用

利用数据挖掘技术,根据WHO-IUIS变应原列表,从Swiss-prot和NCBI,以及国际上现存的变应原数据库、科学文献等,收集、建立了完整的变应原数据库。基于PC机和Linux操作系统,利用相关软件,搭建了致敏性评估网站。利用FastA算法,通过将未知蛋白与数据库中的已知蛋白进行比对,从而判断其致敏性。结果表明构建的网络平台能够加速数据的分析过程。     

A model to estimate growth in young-of-the-year tautog, Tautoga onitis, based on RNA/DNA ratio and seawater temperature

This study presents an indirect method for estimating growth rates of young-of-the-year (YOY) tautog, Tautoga onitis, based on laboratory calibration experiments and nucleic acid-based indices. Field-collected tautog were held in the laboratory at 3 temperatures over a 17-day period. Four feeding levels were used to produce a range of growth rates. An ultraviolet absorption assay was used to measure nucleic acid concentrations in white muscle tissue. The strength of the relationship between growth rate and three nucleic acid-based parameters (RNA concentration, DNA concentration, RNA/DNA ratio (R/D)) was tested. Correlation results indicated a significant positive relationship between R/D and weight-based instantaneous growth rate (G) (r = 0.68; p < 0.001). Both R/D (r = − 0.55; p < 0.006) and RNA (r = − 0.56; p < 0.005) were highly negatively correlated with temperature (T). Multiple linear regression showed that R/D and temperature explained 61% of the variability in growth, resulting in the model G = 0.01285(R/D) + 0.00057(T) − 0.03205 (p < 0.0001). This R/D-temperature model can be used to evaluate recent growth rates in YOY tautog under field conditions and has applications for aquaculture when comparing growth rates of fish held under different culture conditions.     

Near-infrared fluorescence glucose sensing based on glucose/galactose-binding protein coupled to 651-Blue Oxazine

Near-infrared (NIR) fluorescent dyes that are environmentally sensitive or solvatochromic are useful tools for protein labelling in in vivo biosensor applications such as glucose monitoring in diabetes since their spectral properties are mostly independent of tissue autofluorescence and light scattering, and they offer potential for non-invasive analyte sensing. We showed that the fluorophore 651-Blue Oxazine is polarity-sensitive, with a marked reduction in NIR fluorescence on increasing solvent polarity. Mutants of glucose/galactose-binding protein (GBP) used as the glucose receptor were site-specifically and covalently labelled with Blue Oxazine using click chemistry. Mutants H152C/A213R and H152C/A213R/L238S showed fluorescence increases of 15% and 21% on addition of saturating glucose concentrations and binding constants of 6 and 25 mM respectively. Fluorescence responses to glucose were preserved when GBP-Blue Oxazine was immobilised to agarose beads, and the beads were excited by NIR light through a mouse skin preparation studied in vitro. We conclude GBP-Blue Oxazine shows proof-of-concept as a non-invasive continuous glucose sensing system.     

Hierarchical virtual screening of the dual MMP-2/HDAC-6 inhibitors from natural products based on pharmacophore models and molecular docking

The dual-target inhibitors tend to improve the response rate in treating tumors, comparing with the single-target inhibitors. Matrix metalloproteinase-2 (MMP-2) and histone deacetylase-6 (HDAC-6) are attractive targets for cancer therapy. In this study, the hierarchical virtual screening of dual MMP-2/HDAC-6 inhibitors from natural products is investigated. The pharmacophore model of MMP-2 inhibitors is built based on ligands, but the pharmacophore model of HDAC-6 inhibitors is built based on the experimental crystal structures of multiple receptor–ligand complexes. The reliability of these two pharmacophore models is validated subsequently. The hierarchical virtual screening, combining these two different pharmacophore models of MMP-2 and HDAC-6 inhibitors with molecular docking, is carried out to identify the dual MMP-2/HDAC-6 inhibitors from a database of natural products. The four potential dual MMP-2/HDAC-6 inhibitors of natural products, STOCK1 N-46177, STOCK1 N-52245, STOCK1 N-55477, and STOCK1 N-69706, are found. The studies of binding modes show that the screened four natural products can simultaneously well bind with the MMP-2 and HDAC-6 active sites by different kinds of interactions, to inhibit the MMP-2 and HDAC-6 activities. In addition, the ADMET properties of screened four natural products are assessed. These found dual MMP-2/HDAC-6 inhibitors of natural products could serve as the lead compounds for designing the new dual MMP-2/HDAC-6 inhibitors having higher biological activities by carrying out structural modifications and optimizations in the future studies.     

The paleoclimate of the Eastern Mediterranean during the transition from early to mid Pleistocene (900 to 700 ka) based on marine and non-marine records: An integrated overview

Climate change is frequently considered an important driver of hominin evolution and dispersal patterns. The role of climate change in the last phase (900-700 ka) of the Middle Pleistocene Transition (MPT) in the Levant and northeast Africa was examined, using marine and non-marine records. During the MPT the global climate system shifted from a linear 41 k.yr. into a highly non-linear 100 k.yr. system, considerably changing its global modulation. Northeast Africa aridity further intensified around 950 ka, as indicated by a sharp increase in dust flux, and a jump to overall higher levels thereafter, coinciding with a lack of sapropels in the deep eastern Mediterranean (930-690 ka). The increased dust flux centering at ∼800 ka corresponds to the minima in 400 k.yr. eccentricity, a minima in 65 °N solar forcing and in the weakest African monsoon precession periodicity. This resulted in expansion of hyper-arid conditions across North Africa, the lowest lake levels in eastern Africa and the lowest rainfall in the Nile River headwaters. In the eastern Mediterranean an increasing continental signature is seen in glacial stages 22 (∼880 ka) and 20 (∼800 ka). Lower arboreal pollen values also indicate arid conditions during these glacial stages. The southern and eastern parts of the Negev Desert, unlike its northern part, were hyper-arid during the MPT, making them highly unsustainable. The fluctuations in the stands of Lake Amora follow global climate variability but were more moderate than those of its last glacial Lake Lisan successor. In the northern Jordan-Valley Hula Lake, frequent fluctuations in lake level coincide with both global climate changes and minor changes in water salinity varying from fresh to oligohaline. It appears therefore that the most pronounced and widespread deterioration in climate occurred in northeast Africa from 900 to 700 ka, whereas in the Levant the corresponding climatic changes were more moderate.     

Molecular cloning and characterization of a plant alpha1,3/4-fucosidase based on sequence tags from almond fucosidase I

Our work with almond peptide N-glycosidase A made us interested also in the alpha1,3/4-fucosidase which is used as a specific reagent for glycoconjugate analysis. The enzyme was purified to presumed homogeneity by a series of chromatographic steps including dye affinity and fast-performance anion exchange chromatography. The 63 kDa band was analyzed by tandem mass spectrometry which yielded several partial sequences. A homology search retrieved the hypothetical protein Q8GW72 from Arabidopsis thaliana. This protein has recently been described as being specific for alpha1,2-linkages. However, cDNA cloning and expression in Pichia pastoris of the A. thaliana fucosidase showed that it hydrolyzed fucose in 3- and 4-linkage to GlcNAc in Lewis determinants whereas neither 2-linked fucose nor fucose in 3-linkage to the innermost GlcNAc residue were attacked. This first cloning of a plant alpha1,3/4-fucosidase also confirmed the identity of the purified almond enzyme and thus settles the notorious uncertainty about its molecular mass. The alpha1,3/4-fucosidase from Arabidopsis exhibited striking sequence similarity with an enzyme of similar substrate specificity from Streptomyces sp. (Q9Z4I9) and with putative proteins from rice.     

Screening for the selective inhibitors of MMP-9 from natural products based on pharmacophore modeling and molecular docking in combination with bioassay experiment,hybrid QM/MM calculation,and MD simulation

Matrix metalloproteinase-9 (MMP-9) has been considered as an attractive target involving cancer therapy. In this study, the 3D QSAR pharmacophore model of MMP-9 inhibitors is built, and its reliability is subsequently validated based on different methods. The built pharmacophore model consists of the four chemical features, including two hydrogen bond acceptors (HBA), one hydrophobic (HY), and one ring aromatic (RA). Among them, both HY and RA are found to be especially important features because they involve the interactions of inhibitors with the S1′ pocket of MMP-9, which determines the selectivity of MMP-9 inhibitors. By combining pharmacophore model with molecular docking, the virtual screening is carried out to identify the selective MMP-9 inhibitors from natural products. The four potential selective MMP-9 inhibitors of natural products are found. One of them was used to carry out the bioassay experiment inhibiting MMP-9, and the estimated IC₅₀ value of only 26.94 µM clearly shows its strongly inhibitory activity; besides, both the hybrid quantum mechanics/molecular mechanics (QM/MM) calculation and the molecular dynamics simulation are performed to examine the reliability regarding the binding mode of this inhibitor with MMP-9 active sites predicted by molecular docking. All the screened four natural products are found to well bind with the MMP-9 active sites by different kinds of interactions. Finally, the ADMET properties of screened four natural products are assessed. These screened MMP-9 inhibitors of natural products could be used as the lead compounds to perform structural modifications and optimizations in the future work.

Communicated by Ramaswamy H. Sarma