随机走步软聚类识别蛋白质网交叠功能模块

认定蛋白质交互网中的功能模块对于理解细胞的组织结构,处理过程及其功能都是至关重要的。由于一个蛋白质可能具有多重功能因此蛋白质功能模块可能会相互交叠。然而,目前已有的一些识别功能模块的软聚类算法有如下两个缺陷:一是一些算法需要阈值来截断聚类;二是有些算法需要预设聚类数目。为了克服这两个缺陷,提出了随机走步软聚类识别算法来认定蛋白质交互网中的交叠功能模块。实验结果表明该算法在无需任何参数的情况下能发现一些重要的交叠功能模块。

一种基于多头注意力机制的关键蛋白质靶点识别方法

蛋白质是机体功能的重要执行者。特定的一些蛋白质对生物的生存、繁殖和生理调节尤为关键,它们往往成为疾病发生、发展中的重要参与者,这类蛋白质被称为关键蛋白质。因此,在疾病预防和治疗过程中快速找到蛋白质关键靶点是尤为重要的。本文提出了一种借助多头注意力机制来解决这一难题的方法。该方法将蛋白质相互作用(PPI)网络的拓扑特征、基因表达谱特征以及同源特融合,从而构建一个融合PPI网络。进而,我们采用图注意力神经网络(GAT)模型,学习融合PPI网络中节点的特征表示,为了更好的地捕获蛋白质之间的关联关系,我们引入多头注意力机制增强模型的学习效果。最终,通过在DIP酵母蛋白数据集上的训练和测试,实验结果证明了我们的方法相较于传统的基于拓扑的策略具有更高的识别精度。

基于贪婪算法的疾病相关蛋白质子网搜索

各种研究结果不断证明,人类各种常见疾病都属于复杂疾病,是由多基因、多因素、遗传和环境共同作用的结果。借助于高通量生物技术的飞速发展,生物学家建立起了蛋白交互网络,如果借助复杂网络研究的方法,从这些网络中找出与疾病相关的蛋白质子网络,将有助于我们更深入地了解生物体的运作机制。本文提出了一种基于贪婪算法的搜索方法,能够自动地搜索整个网络中的子网或模块,并且能够结合芯片数据同时进行T检验来判断子网络对疾病表型的区分能力。通过计算子网的P值,给出该蛋白质子网络的统计显著性值并进行区分能力排序。运行结果表明,本方法不但能够用于发现已知的疾病蛋白,而且能够对未知的蛋白进行预测,结合生物芯片技术,将会对疾病基因的研究提供有价值的信息。

基于蛋白质互作评价差异表达基因的重复性

利用高通量基因表达谱数据可以识别在肿瘤与正常组织中差异表达的基因,为研究癌机理提供重要的线索。目前,在研究同种癌型的不同实验中发现的差异表达基因的交叠比例很低。这种高通量基因表达谱数据低重复性的现象严重制约了基因芯片在癌症研究中的应用。然而,已有研究表明从研究同种癌型的不同实验数据中得到的不交叠的差异表达基因倾向于扰动相同的功能。因此,在评价差异表达基因重复性时,应考虑其在生物学功能上的一致性。本文结合基因共表达和蛋白质互作关系,设计了功能重复性指标来评价差异表达基因列表的可重复性。通过分析两套卵巢癌数据,发现对同种癌型得到的差异表达基因具有很高的功能一致性(p<0.0001)。结果表明,在功能水平上评估差异表达基因的一致性具有合理性。

基于降维的蛋白质不相关功能预测

蛋白质是生命活动的重要物质基础,对其功能的准确标注可以极大地促进生命科学的研究与发展.已有的蛋白质功能预测方法通常仅关注利用蛋白质具有某些功能的信息(正样例),并没有关注利用蛋白质不相关的功能信息(负样例).已有研究表明,结合蛋白质负样例可以降低蛋白质功能预测的复杂度并提高预测精度.本文提出一种基于降维的蛋白质不相关功能预测方法 (predicting irrelevant functions of proteins based on dimensionality reduction,IFDR).IFDR通过在蛋白质互作网邻接矩阵和蛋白质–功能标记关联矩阵上分别进行随机游走,挖掘蛋白质之间的内在关系和预估蛋白质的缺失功能标记,再分别利用奇异值分解将上述2个矩阵投影降维为低维实数矩阵,最后利用半监督回归预测负样例.在酵母菌、人类和拟南芥的蛋白质数据集上的实验表明,IFDR比已有相关算法能够更准确地预测负样例,对互作网络和功能标记空间的降维均可以提高负样例预测精度.

基于有向混合图的蛋白质新功能预测

蛋白质执行着生物体内各种重要生物活动,对蛋白质功能的准确标注能极大地促进生命科学研究与应用.传统的湿实验法通量低,已无法测定高通量技术产生的海量蛋白质功能,基于计算模型的大规模蛋白质功能预测是后基因时代生物信息学的核心任务之一.当前基于机器学习的方法通常仅关注对完全未标记功能的蛋白质的功能预测,而忽略了已标注功能的蛋白质可能存在的自身功能标记的不完整性,预测精度有限.本文结合基因本体层次结构关系和蛋白质互作网信息,设计了一种有向混合图(directed hybrid graph,d HG)对上述信息进行描述,并在此基础上提出一种基于有向混合图重启动随机游走的蛋白质功能预测方法——d HG.本文提出的d HG方法不仅能补充已知部分功能标记的蛋白质新功能,还能预测功能完全未知的蛋白质新功能.在酵母菌和人类蛋白质上的实验结果表明,d HG在多种评价度量上的预测性能均优于现有方法,且效率更高.

基于0-1矩阵分解的蛋白质功能预测

准确地标注蛋白质功能是功能基因组学的核心任务之一.蛋白质功能标注信息存在大量缺失且功能标签空间巨大.近期一些标签压缩方法被提出并应用于蛋白质功能预测,但是这些方法获取的压缩标签可解释性差,且面临着多标记学习中的阈值划分难题.为解决这些问题,本文提出一种基于0-1矩阵分解的蛋白质功能预测方法 (zero-one matrix factorization, ZOMF). ZOMF首先将蛋白质–功能标签关联矩阵分解成两个低秩0-1矩阵,挖掘蛋白质和功能标签间的内在关联.其次它利用蛋白质互作网和基因本体结构信息分别针对上述两个低秩矩阵定义了平滑正则项,约束指导低秩矩阵的优化.最后它利用优化获取的低秩矩阵重构关联矩阵,进而实现蛋白质功能预测.通过在酵母菌、拟南芥、老鼠和人类数据集上的实验表明, ZOMF比已有的相关算法能够更准确地预测蛋白质功能,它无需对重构的关联矩阵进行阈值划分,压缩的0-1标签可解释性更直观.

巴西橡胶树乳管伤口堵塞物形成调节的研究进展

巴西橡胶树是天然橡胶的主要来源,割胶是从橡胶树中获取天然橡胶的唯一途径。割胶后乳管伤口堵塞物的形成使排胶速度迅速降低,产量减少。对堵塞物的形成和调控的研究不仅具有重要的理论意义,也具有重要的应用价值。本文从堵塞物对排胶的影响、堵塞物的成分、堵塞物形成和调控的相关因素等方面进行了综述,为橡胶树排胶生理学的深入研究提供参考。

Increasing Accumulation Level of Foreign Protein in Transgenic Plants Through Protein Targeting

Targeting of the synthesized polypeptide in the cells is an important research field in modern cell biology. Cowpea trypsin inhibitor (cpti) gene has been modified and a fusion protein gene (sck) was produced by fusing a signal peptide sequence at cpti 5' end and an endoplasm reticulum (ER) retention signal peptide at cpti3' end respectively. The signal peptide can direct the newly synthesized polypeptide into ER, while ER retention signal can make the protein retained in the ER and its derivative protein body. ELISA test indicated that the accumulation level of foreign CpTI protein in sck transgenic tobacco (Nicotiana tabacum L.) was two times higher than cpti transgenic tobaccos and some individuals were four times higher. At the same time, sck transgenic tobacco has a high resistance to Lepidoptera pest due to the increased accumulation level of foreign CpTI protein. The strategy of foreign protein targeting can be used to increase the accumulation level of foreign protein in transgenic plants and can be widely applied to other related research field in plant genetic engineering.

Molecular Cloning the Gene of Small Heat Shock Protein in the Mitochondria and Endoplasmic Reticulum of Tomato

A cDNA Library was constructed with the heat shocked tomato ( Lycopersicon esculentum Mill.) flowers and then was screened with the probes of mitochondrial and endoplasmic reticulum conservative regions that were cloned by using RT-PCR. The complete cDNAs of mitochondrial and endoplasmic reticulum small heat shock protein ( shsp) were selected out from the cDNA library. Furthermore, the temperature responses of these shsp genes were determined. Northern hybridization showed that the heat response temperatures of both genes in tomato flower were lower than that in leaf and that mitochondria shsp in leaf was cold-inducible. In this paper, the molecular features of the cloned genes, the causes of the uncommon heat response temperatures of sHSP in newer and the cold inducible character of mitochondria shsp gene in leaf were discussed.

The Life of a Protein Molecule——Protein Quality Control

The research progress in molecular chaperones, unfolded protein response （UPR） and ER-associated degradation （ERAD） involved in the protein quality control was summarized in this paper, and then the existing problems and the future devel- opment prospect were also discussed. It was pointed out that the life process of protein experienced four stages including synthesizing, folding, assembling and degradation, while each stage required strict quality control. In endoplasmic reticulum （ER）, a variety of proteins had been synthesized, folded and modified to form func- tional proteins with certain conformation. When the folding was blocked in ER, the unfolded proteins would aggregate and induce the UPR, which up-regulated the level of modification enzymes folded by a series of molecular chaperones and proteins to help them accomplish folding and assembling. If these proteins were still folded incorrectly, they would enter into ERAD for being degraded.

The retromer component SNX6 interacts with dynactin p150Glued and mediates endosome-to-TGN transport

The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the trans-Golgi network （TGN）. It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps35 and a membrane-binding coat subcomplex of sorting nexins （SNXs）. Previous studies identified SNX1/2 as one of the components of the SNX subcomplex, and SNX5/6 as candidates for the second SNX. How the retromer-associated cargoes are recognized and transported by molecular motors are largely unknown. In this study, we found that one of SNX1/2＇s dimerization partners, SNX6, interacts with the p150Gued subunit of the dynein/dynactin motor complex. We present evidence that SNX6 is a component of the retromer, and that recruitment of the motor complex to the membrane-associated retromer requires the SNX6-pl50Gued interaction. Disruption of the SNX6-pl50Glued interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. These observations indicate that in addition to SNX1/2, SNX6 in association with the dynein/dynactin complex drives the formation and movement of tubular retrograde intermediates.

Endocytosis of FcαR is clathrin and dynamin dependent, but its cytoplasmic domain is not required

FcαR, the Fc receptor for IgA, is essential for IgA-mediated immune responses. Previous studies have shown that IgA and IgA immune complexes can be rapidly endocytosed by FcαR. However, the underlying mechanism remains unclear. Here, we investigated the endocytic pathway of FcαR in monocytic cell line, U937, that naturally express FcuR and in transfected Chinese hamster ovary （CHO）, COS-7 and Hela cells. By using selective chemical inhibitors of different endocytic pathways, overexpression of dominant-negative mutants of Eps15 and knockdown of clathrin heavy chain （CHC） via RNA interference, we demonstrated that endocytosis of FcaR was through a clathrin-mediated pathway. The endocytosed FcαR went into Rab5- and Rabll-positive endosomes. However, endocytosis of FcaR could not be blocked by a dominant-negative mutant of Rab5. We also demonstrated that endocytosis of FcαR was dynamin-dependent by overexpressing a dominant-negative mutant of dynamin. The potential endocytic motif for FcαR was also examined. Unexpectedly, we found that the entire cytoplasmic domain of FcaR was not required for the endocytic process of FcαR. We conclude that endocytosis of FcaR is clathrin- and dynamin-dependent, but is not regulated by RabS, and the endocytic motif is not located in the cytoplasmic domain of FcαR.

Integrated analysis of micro RNA and m RNA expression profiles in HBx-expressing hepatic cells

AIM To identify the miRNA-mRNA regulatory network in hepatitis B virus X (HBx)-expressing hepatic cells. METHODS A stable HBx-expressing human liver cell line L02 was established. The mRNA and miRNA expression profiles of L02/HBx and L02/pcDNA liver cells were identified by RNA-sequencing analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed to investigate the function of candidate biomarkers, and the relationship between miRNA and mRNA was studied by network analysis. RESULTS Compared with L02/pcDNA cells, 742 unregulated genes and 501 downregulated genes were determined as differentially expressed in L02/HBx cells. Gene ontology analysis suggested that the differentially expressed genes were relevant to different processes. Concurrently, 22 differential miRNAs were also determined in L02/HBx cells. Furthermore, integrated analysis of miRNA and mRNA expression profiles identified a core miRNA-mRNA regulatory network that is correlated with the carcinogenic role of HBx. CONCLUSION Collectively, the miRNA-mRNA network-based analysis could be useful to elucidate the potential role of HBx in liver cell malignant transformation and shed light on the underlying molecular mechanism and novel therapy targets for hepatocellular carcinoma.

Cloning and characterization of a novel gene encoding a putative seven-span transmembrane protein localized in endoplasmic reticulum

Objective: To clone and analyze the structure of a novel gene, named EST 1 (endoplasmic reticulum localized seven span transmembrane protein 1) and to analyze the expression pattern and intracellular location of EST 1. Methods: The cDNA library was screened to isolate novel cDNA fragment. The structure of novel gene was analysed by computer software. Expression of EST 1 was analyzed by dot blot and Northern blotting. Intracellular localization was observed after EST 1 enhanced green fluorescence protein (EGFP) fusion gene was transfected into mammalian cells. Results: The full length cDNA of mouse EST 1 was 1 802 bp, with a 1 293 bp open reading frame encoding 431 amino acids. It was predicated that protein encoded by EST 1 contained a signal peptide sequence at the N terminus, seven putative transmembrane domains, and an ER retaining signal at the C terminus. EST 1 EGFP fusion protein showed an ER like intracellular distribution in mammalian cells. Expression pattern analysis showed that EST 1 is expressed in all tissues examined. Conclusion: EST 1 is encoding a putative seven span transmembrane protein localized in endoplasmic reticulum. EST 1 was expressed in all tissues examined, suggesting an essential function of EST 1 in cells.

Study progress of cell endocytosis

Endocytosis is a process through which extracellular materials are transported into cell through membrane deformation. This process is not a simple step-by-step process in which a series of proteins function according to the chronological order, but rather a complex process comprising many members which are regulated precisely. The role of endocytosis is broadly divided into two categories, phagocytosis and pinocytosis, the latter is divided into four species in accordance with the size of endocytosis substances： clathrin dependent endocytosis, the diameter of clathrin-coated vesicle is 100-150 nm; caveolin dependent endocytosis, the diameter of caveolin protein-coated vesicle is 50-100 nm; macropinocytosis, the diam- eter of macropinocytosis is generally 0.5-2 μm, sometimes up to 5 μm; clathrin and caveolin independent endocytosis. Many proteins including endophilin A1, A2, A3, and endocytotic proteins B, B1a, and Blb as well as dynamin, actin and Rab protein families are involved in endocytosis and play an important role in different stages. The abnormal endocytosis may be involved in the development of certain diseases.

Analysis of mechanism on Indigo Naturalis in treating chronic myelocytic leukemia based on two-dimentional model of protein-protein interaction network-moleculardocking technique

To explore the molecular mechanism of Ind-igo Naturalis in intervening chronic myelocytic leukemia （CML） under the guidance of protein-protein interaction network, the molecular docking technique and in vitro cell experiment were chosen. CML-related genes were obtained from the online mendelian inheritance in man database （OMIM）, then String 10. 0 was used for text mining and constructing the CML protein-protein interaction network. The interaction data were input in Cytoscape 3. 4. 0 software. Plug-in CentiScaPe 2. 1 was used for implement topology analysis. Small active substances of Indigo Naturalis were obtained from a third-party database, which were optimized by Chemoffice 8. 0 and Sybyl 8. 1, then small molecular ligand library was obtained. The molecular docking was carried out by Surflex-Dock module, the key target was received after scoring. Protein-protein interaction network of CML was constructed, which was consisted of 425 nodes （ proteins） and 2 799 sides （ interactions）. The key gene J.AK2 was got. CML is a polygenic disease and JAK2 is likely to be a key node.

Development of Bioinfo-Portal Tool for the Analysis of Genomic and Proteomic Data

The recent explosion of biological data and the concomitant proliferation of distributed databases make it challenging for biologists and bioinformaticians to discover the best data resources for their needs, and the most efficient way to access and use them For the biologist, running bioinformatics analyses involve a time-consuming management of data and tools. Users need support to organize their work, retrieve parameters and reproduce their analyses. They also need to be able to combine their analytic tools using a safe data flow software mechanism. Finally we have designed a system, Bioinfo-Portal, to provide a flexible and usable web environment for defining and running bioinformatics analyses. It embeds simple yet powerful data management features that allow the user to reproduce analyses and to combine tools using an adobe flex tool. Bioinfo-Portal can also act as a front end to provide a unified view of already-existing collections of bioinformatics resources. Users can analyze genomic and proteomic data by using the tools that has been integrated in the portal （tools for alignments, dotplots, motif detection, domain analysis, profile searching and tertiary structure prediction）. The sequences that user obtained from portal＇s nucleotide and protein databases are easily analyzed by the portal tools on the same interface in no time. User can also take benefit from the animations.

Tools for Protein Structure Prediction at the bri-shur.com Web Portal

lntemet services on bioinformatics still remain a popular tool for the researchers. Here the authors present a recently developed web-site http：//bri-shur.com where several tools and pipelines for protein structure prediction are implemented. The prediction of a structure for a particular protein often requires a sensitive and iterative approach, and the web-site provides an environment for this kind of work. Software that is used in the services includes both free programs available in the Internet and newly developed algorithms. The service on homology screening in PDB for a structure template is implemented using an approach that is alternative to well-known BLAST algorithm and it has some advantages over BLAST. The service on homology modeling uses well-known Nest program. The service on protein energy estimate allows selecting a best template in the set of homologs and adds a functionality of fold recognition to the environment. The design of the site simplifies several of the most useful bioinformatics routines, thus making them available to a large community of researchers. Services are provided free of charge without registration, and the user＇s privacy is taken care of.

Population Bursts of Parvalbumin-Positive Interneurons Inhibit Spiking Pyramidal Cells in Spontaneously Active Cortical in Vitro Networks

Author present the interplay between different neuron types in the spontaneous electrical activity of low density cortical in vitro networks grown on MEA （multielectrode arrays） of glass neurochips. In 10% of the networks, the continuously spiking activity of some neurons was inhibited by synchronous bursts or superbursts of the majority of the other neurons. Immunohistochemical staining subsequent to MEA recordings suggest that the synchronously bursting neurons are parvalbumin-positive interneurons with abundant axonal ramifications. Blocking chemical synaptic transmission by Ca2＋-free medium revealed that the curbed spiking neurons are intrinsically active. It is assumed that these neurons are pyramidal cells which may be inhibited by groups of synchronously bursting interneurons. It is propose that the observed burst-induced inhibition is an important principle in the temporal organization of neuronal activity as well as in the restriction of excitation, and thus essential for information processing in the cerebral cortex.