Gene function prediction based on Gene Ontology Hierarchy Preserving Hashing

Gene Ontology (GO) uses structured vocabularies (or terms) to describe the molecular functions, biological roles, and cellular locations of gene products in a hierarchical ontology. GO annotations associate genes with GO terms and indicate the given gene products carrying out the biological functions described by the relevant terms. However, predicting correct GO annotations for genes from a massive set of GO terms as defined by GO is a difficult challenge. To combat with this challenge, we introduce a Gene Ontology Hierarchy Preserving Hashing (HPHash) based semantic method for gene function prediction. HPHash firstly measures the taxonomic similarity between GO terms. It then uses a hierarchy preserving hashing technique to keep the hierarchical order between GO terms, and to optimize a series of hashing functions to encode massive GO terms via compact binary codes. After that, HPHash utilizes these hashing functions to project the gene-term association matrix into a low-dimensional one and performs semantic similarity based gene function prediction in the low-dimensional space. Experimental results on three model species (Homo sapiens, Mus musculus and Rattus norvegicus) for interspecies gene function prediction show that HPHash performs better than other related approaches and it is robust to the number of hash functions. In addition, we also take HPHash as a plugin for BLAST based gene function prediction. From the experimental results, HPHash again significantly improves the prediction performance. The codes of HPHash are available at: http://mlda.swu.edu.cn/codes.php?name=HPHash.     

分枝杆菌glpX基因的功能

摘要:【目的】构建耻垢分枝杆菌(Mycobacterium smegmatis)glpX基因敲除株,研究其在生理代谢中的功能。【方法】利用分枝杆菌噬菌体Che9c重组系统构建耻垢分枝杆菌glpX 基因敲除株;比较野生株及突变株在不同碳源培养条件下的生长差异;通过荧光实时定量PCR,比较野生株在以葡萄糖或油酸为唯一碳源培养下,glpX基因的表达水平。【结果】glpX突变株在以甘油或油酸为唯一碳源的培养基中无法生长;野生株在以油酸为唯一碳源培养下,glpX基因表达上调。【结论】glpX基因编码了分枝杆菌糖异生途径必需的和非冗余的果糖1,6-二磷酸酶(fructose 1,6-bisphosphatase,FBPase)。     

Gene function identified by interspecific transformation

Aspergillus nidulans is able to utilize 2-pyrrolidinone as a nitrogen source while two related Aspergillus species, A. niger and A. terreus, cannot. Mutations in the lamA gene of A. nidulans prevent growth on 2-pyrrolidinone. A plasmid (pLAM7) has been isolated containing the A. nidulans lamA gene and a divergently transcribed adjacent gene of unknown function. Transformation of A. terreus with subclones of pLAM7 showed that both genes are essential for the utilization of a new nitrogen source, 2-pyrrolidinone, in that species. The previously unidentified gene has been designated lamB.     

Gene prophylaxis by a DNA repair function

Gene therapy, the treatment of disorders or pathophysiologic states on the basis of the transfer of genetic information, has been thoroughly investigated for the treatment of lung illnesses, e.g. cystic fibrosis, alpha1-antitrypsin deficiency-related emphysema and cancer. Transfer of genetic information may be further used to elevate the level of protection of normal lung tissues in at risk individuals, with preventing purposes. This concept can be described by the term "gene prophylaxis". Lying at the gas-exchange interface, lung epithelia may be at risk of oxidation-induced mutagenesis. Further, inflammation processes possibly consequent on smoking liberate reactive oxygen species (ROS) that multiply the carcinogenic effects of tobacco. Some studies report in lung cancer patients an high frequency of variations of the 8-oxoguanine DNA glycosylase (hOGG1) gene that encodes a sluggish glycosylase for oxidized purines. Unlike dietary interventions with antioxidant drugs that only allow temporary oxy-radical scavenging, reinforcing the DNA repair capacity in lung epithelia may afford long-term, steady protection from ROS-generated mutagenesis and carcinogenesis. In this regard, the Escherichia coli formamidopyrimidine DNA glycosylase (FPG) is a possible tool. FPG is 80-fold faster than hOGG1 in repairing oxidized purines and has broader substrate specificity. Cell culture studies have shown that FPG can be expressed in mammalian cells where it accelerates DNA repair and abates mutagenicity of a wide range of DNA damaging agents. Spontaneous mutagenesis drops too. Prophylaxis of oxidative DNA damage and mutation could be achieved in lung epithelia and other tissues of at-risk individuals by FPG expression. Currently available vehicles for this peculiar type of gene therapy are briefly surveyed.     

Gene function of heterozygotes in phage T4

Summary Gene function of various T4-heterozygotes was tested. About half of the HETs containing wild type and anam-mutation disappeared under non-permissive conditions, if theam-defect concerned early functions. The same was found when phages, heterozygous forr ⁺ and anrII-point-mutation, were adsorbed to K12 (). A much more extensive loss of HETs in K could be observed if anrIIA- and anrIIB-point-mutation (block-mutations showed different results) occurred together in a non-recombinant heterozygote. The findings provide evidence that one class of T4-heterozygotes has a heteroduplex DNA-structure.With 3 Figures in the Text     

Gene structure and function of granulocyte colony-stimulating factor

In the last few years, the molecular and genetic nature of the granulocyte colony-stimulating factor, which controls proliferation and differentiation of neutrophils, has been characterized. Recent clinical application of G-CSF proves that this hormone is effective in the treatment of patients suffering from neutropenia.     

Gene function prediction using labeled and unlabeled data

Background  

In general, gene function prediction can be formalized as a classification problem based on machine learning technique. Usually, both labeled positive and negative samples are needed to train the classifier. For the problem of gene function prediction, however, the available information is only about positive samples. In other words, we know which genes have the function of interested, while it is generally unclear which genes do not have the function, i.e. the negative samples. If all the genes outside of the target functional family are seen as negative samples, the imbalanced problem will arise because there are only a relatively small number of genes annotated in each family. Furthermore, the classifier may be degraded by the false negatives in the heuristically generated negative samples.     

Gene topography and function. I. Gene expression in germinating conidia of Neurospora crassa

In an attempt to find clues for the significance of the gene ordering along the eukaryotic chromosome, a system consisting of germinating conida of Neurospora crassa was studied. Thirteen enzyme activities corresponding to genes widely distributed on five chromosomes were determined in dormant and in germinating conidia. Ten of these enzymes showed lower activities in the resting state, and the time patterns of their increase were determined during germination. The results obtained do not support a scheme of sequential expression of genes during the emergence from dormancy as a counterpart of the sequence of the corresponding genes along the chromosome. Two of the loci studied were analyzed both in the normal (wild-type) ordering and in a translocated position in which the two genes are located in an inverted order respective to the centromere and farther apart from it. The altered order of the genes did not influence significantly the time and pattern of increase in the activities of the corresponding enzymes.     

Gene silencing quantitatively controls the function of a developmental trans-activator

How a single cell gives rise to progeny with differing fates remains poorly understood. We examined cells lacking methyl CpG binding domain protein-2 (MBD2), a molecule that has been proposed to link DNA methylation to silent chromatin. Helper T cells from Mbd2(-/-) mice exhibit disordered differentiation. IL-4, the signature of a restricted set of progeny, is expressed ectopically in Mbd2(-/-) parent and daughter cells. Loss of MBD2-mediated silencing renders the normally essential activator, Gata-3, dispensable for IL-4 induction. Gata-3 and MBD2 act in competition, wherein each factor independently, and quantitatively, regulates the binary choice of whether heritable IL-4 expression is established. Gata-3 functions, in part, to displace MBD2 from methylated DNA. These results suggest that activating and silencing signals integrate to provide spatially and temporally restricted patterns of gene activity.     

Gene delivery for genetically engineered mucosal cells with enhanced function

A non-viral transfection method for oral mucosal cells was investigated using a modified transfection method and five commercial transfection reagents. The CellFECTIN^TM gave the highest expression of a transfected gene. When the mucosal cells were transfected with 0.3 ng DNA/cell, the transfection efficiency was optimal, and the production of a reporter protein increased up to ten times higher than those with the other transfection reagents.     

Gene expression regulation and domain function of hematopoietic GATA factors

The hierarchical gene regulatory network in hematopoiesis is highly complex, making elucidation of the processes of specification and differentiation of hematopoietic cells a challenging task. Recent discoveries have divulged the GATA factors as central to the genetic control of hematopoiesis. In particular, hematopoietic development is subject to extensive and precise regulation of GATA-1 and GATA-2 at the molecular level. We wish to emphasize the regulatory relationships between GATA-1 and GATA-2 implicated in cell development. An advanced experimental genetic approach has provided evidence that abnormalities in this network may result in a variety of blood disorders. The most striking new finding is the novel pathogenesis arising from GATA-1 dysfunction that leads to leukemia.