基于遗传算法的基因分类

独立分量分析(ICA)是应用于基因分类的一种统计方法.但独立分量分析中的估计分离矩阵算法主要采用了随机梯度算法、自然梯度算法,这些基于梯度下降的寻优算法很容易陷入局部极值,所得结果不精确.本文提出了一种基于遗传算法的基因分类算法,其基本思想是利用遗传算法代替独立分量分析中的传统的估计分离矩阵算法,对基因表达式数据进行分类,从而克服了结果不精确的问题.分析和实验结果表明,该分类方法获得了更好的分类效果.

Gene expression profile in H4IIE rat hepatoma cells exposed to an antifouling booster biocide Irgarol-1051 degradation product

To better understand the toxicity of an antifouling booster biocide Irgarol-1051 degradation product M2 3-4-tert-butylamino-6-methylthiol-s-triazin-2-ylamino pro-pionaldehyde this study utilized a DNA microarray technique to explore the genotoxicity of M2. The Affymetrix Inc. rat genome 230 2.0 GeneChip was employed to examine alterations in gene regulation in rat hepatoma cells exposed to 30 μmol/L of M2 for 96 h.The results showed that 38 genes were significantly p＆lt;0.002 5 altered by M2 at two-fold changes in all the four possible control/exposure comparisons. Accn5 was the only well described gene consistently being suppressed which likely altered the epithelial sodium channel ENaC .10 and 82 annotated genes were up-and down-regulated in at least one of the control/exposure comparisons respectively. The induced genes were mainly involved in the nucleus belonging to the cellular component. The largest categories of suppression concerned G-protein coupled receptor protein signaling pathways belonging to the biological process and integral to membranes belonging to the cellular component.

Gene expression profile of esophageal cancer in North East India by cDNA microarray analysis

AIM： To identify alterations in genes and molecular functional pathways in esophageal cancer in a high incidence region of India where there is a widespread use of tobacco and betel quid with fermented areca nuts. METHODS： Total RNA was isolated from tumor and matched normal tissue of 16 patients with esophageal squamous cell carcinoma. Pooled tumor tissue RNA was labeled with Cy3-dUTP and pooled normal tissue RNA was labeled with Cy5-dUTP by direct labeling method. The labeled probes were hybridized with human 10K cDNA chip and expression profiles were analyzed by Genespring GX V 7.3 （Silicon Genetics）. RESULTS： Nine hundred twenty three genes were differentially expressed. Of these, 611 genes were upregulated and 312 genes were downregulated. Using stringent criteria （P ≤ 0.05 and ≥ 1.5 fold change）, 127 differentially expressed genes （87 upregulated and 40 downregulated） were identified in tumor tissue. On the basis of Gene Ontology, four different molecular functional pathways （HAPK pathway, G-protein coupled receptor family, ion transport activity, and serine or threonine kinase activity）were most significantly upregulated and six different molecular functional pathways （structural constituent of ribosome, endopeptidase inhibitor activity, structural constituent of cytoskeleton, antioxidant activity, acyl group transferase activity, eukaryotic translation elongation factor activity）were most significantly downregulated. CONCLUSION： Several genes that showed alterations in our study have also been reported from a high incidence area of esophageal cancer in China. This indicates that molecular profiles of esophageal cancer in these two different geographic locations are highly consistent.

Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response

Over the past 5 years there has been a rapid increase in the use of microarray technology in the field of cancer research, The majority of studies use microarray analysis of tumor biopsies for profiling of molecular characteristics in an attempt to produce robust classifiers for prognosis. There are now several published gene sets that have been shown to predict for aggressive forms of breast cancer, where patients are most likely to benefit from adjuvant chemotherapy and tumors most likely to develop distant metastases, or be resistant to treatment. The number of publications relating to the use of microarrays for analysis of normal tissue damage, after cancer treatment or genotoxic exposure, is much more limited. A PublVled literature search was conducted using the following keywords and combination of terms： radiation, normal tissue, microarray, gene expression profiling, prediction. With respect to normal tissue radiation injury, microarrays have been used in three ways： （1） to generate gene signatures to identify sensitive and resistant populations （prognosis）; （2） to identify sets of biomarker genes for estimating radiation exposure, either accidental or as a result of terrorist attack （diagnosis）; （3） to identify genes and pathways involved in tissue response to injury （mechanistic）. In this article we will review all （relevant） papers that covered our literature search criteria on microarray technology as it has been applied to normal tissue radiation biology and discuss how successful this has been in defining predisposition markers for radiation sensitivity or how it has helped us to unravel molecular mechanisms leading to acute and late tissue toxicity. We also discuss some of the problems and limitations in application and interpretation of such data.

Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells

AIM:To investigate the effects of four probiotic bacteria and their combination on human mast cell gene expression using microarray analysis.METHODS:Human peripheral-blood-derived mast cells were stimulated with Lactobacillus rhamnosus (L.rhamnosus) GG (LGG),L.rhamnosus Lc705 (Lc705),Propionibacterium freudenreichii ssp.shermanii JS (PJS) and Bifidobacterium animalis ssp.lactis Bb12 (Bb12) and their combination for 3 or 24 h,and were subjected to global microarray analysis using an Affymetrix GeneChip Human Genome U133 Plus 2.0 Array.The gene expression differences between unstimulated and bacteria-stimulated samples were further analyzed with GOrilla Gene Enrichment Analysis and Visualization Tool and MeV Multiexperiment Viewer-tool.RESULTS:LGG and Lc705 were observed to suppress genes that encoded allergy-related high-affinity IgE receptor subunits α and γ (FCER1A and FCER1G,respectively) and histamine H4 receptor.LGG,Lc705 and the combination of four probiotics had the strongest effect on the expression of genes involved in mast cell immune system regulation,and on several genes that encoded proteins with a pro-inflammatory impact,such as interleukin (IL)-8 and tumour necrosis factor alpha.Also genes that encoded proteins with anti-inflammatory functions,such as IL-10,were upregulated.CONCLUSION:Certain probiotic bacteria might diminish mast cell allergy-related activation by downregulation of the expression of high-affinity IgE and histamine receptor genes,and by inducing a pro-inflammatory response.

Classification analysis of microarray data based on ontological engineering

Background knowledge is important for data mining, especially in complicated situation. Ontological engineering is the successor of knowledge engineering. The sharable knowledge bases built on ontology can be used to provide background knowledge to direct the process of data mining. This paper gives a common introduction to the method and presents a practical analysis example using SVM (support vector machine) as the classifier. Gene Ontology and the accompanying annotations compose a big knowledge base, on which many researches have been carried out. Microarray dataset is the output of DNA chip. With the help of Gene Ontology we present a more elaborate analysis on microarray data than former researchers. The method can also be used in other fields with similar scenario.

Microarray-based analysis for hepatocellular carcinoma: From gene expression profiling to new challenges

Accumulation of mutations and alterations in the expression of various genes result in carcinogenesis,and the development of microarray technology has enabled us to identify the comprehensive gene expression alterations in oncogenesis.Many studies have applied this technology for hepatocellular carcinoma(HCC),and identified a number of candidate genes useful as biomarkers in cancer staging,prediction of recurrence and prognosis,and treatment selection.Some of these target molecules have been used to develop new serum diagnostic markers and therapeutic targets against HCC to benefit patients.Previously,we compared gene expression profiling data with classification based on clinicopathological features,such as hepatitis viral infection or liver cancer progression.The next era of gene expression analysis will require systematic integration of expression profiles with other types of biological information,such as genomic locus,gene function,and sequence information.We have reported integration between expression profiles and locus information,which is effective in detecting structural genomic abnormalities,such as chromosomal gains and losses,in which we showed that gene expression profiles are subject to chromosomal bias.Furthermore,array-based comparative genomic hybridization analysis and allelic dosage analysis using genotyping arrays for HCC were also reviewed,with comparison of conventional methods.

cDNA array screening differentially expressed gene in liver regeneration

Objective: To screen the differentially expressed gene in liver regeneration with cDNA array and gain insight of the pathogenesis of the acute hepatic failure. Methods: Acute liver failure model in Sprague-Dawley (SD) rat was induced by 95% hepatectomy. The differential expression profiles in regenerating rat liver were studied by a cDNA array representing 1176 cDNA clusters. Some genes were randomly selected from a pool of differentially expressed genes and subjected to RT-PCR to further confirm the result from microarray hybridization. Results: The alterations of transcription levels were noted in the expressions of 188 genes. There were 138 genes with their expression up-regulated such as growth factors, PCNA, ribosomal proteins, IL6 and CDKs which were associated with cell cycle regulation, stress, metabolism and proliferation. Conclusion: cDNA array is a powerful tool to explore the gene expression of acute liver failure and is potential for the diagnosis and treatment of liver regeneration.

Studies of Differentially-Expressed Genes in Human Endometrial Cancer of Various Differentiated Grades

OBJECTIVE To study the gene expression profiles of human endometrial cancers at various differentia0ted grade levels and to identify the genes related to differentiation of the endometrial cancers. METHODS cDNA microarray technology was used to analyze the differentially-expressed genes among different differentiated grades of 32 cases of endometrial cancer. Hierarchical cluster analysis （HCA） for the gene expression profiles of the cases was employed. RESULTS The tissue samples were grouped based on the various differentiated tumor grades with 33 differentiation-related genes identified out （P〈0.001）. Based on the results from the HCA, the conformity rate was 91% among the 33 differentially-expressed genes, and the analysis of pathological classification.CONCLUSION Genes related to the differentiation of endometrial cancer can be identified by using gene chips to analyze the expression profiles of endometrial cancers at various differentiated grades; HCA of the gene expression profiles can be helpful for distinguishing high-risk endometrial cancers before surgery.

Identification of differential gene expressions in colorectal cancer and polyp by cDNA microarray

AIM： TO screen the differential expressed genes in colorectal cancer and polyp tissue samples. METHODS： Tissue specimens containing 16 cases of colorectal adenocarcinoma and colorectal polyp vs nor- mal mucosae were collected and subjected to cDNA microarray and bioinformatical analyses. Quantitative reverse transcription-polymerase chain reaction （qRT- PCR） was used to confirm some of the cDNA microarray data.RESULTS： The experimental data showed that eight genes were differentially expressed, most of which were upregulated in adenomatous polyp lesions. Forty-six genes expressions were altered in colorectal cancers, of which 29 were upregulated and 17 downregulated, as compared to the normal mucosae. In addition, 18 genes were similarly altered in both adenomatous polyps and colorectal cancer, qRT-PCR analyses confirmed the cDNA microarray data for four of those 18 genes： MTA1, PDCD4, TSC1 and PDGFRA. CONCLUSION： These differentially expressed genes likely represent biomarkers for early detection of co- Iorectal cancer and may be potential therapeutic targets after confirmed by further studies.

Normalization strategy of microarray gene expression data

Objective： To discuss strategies and methods of normalization on how to deal with and analyze data for different chips with the combination of statistics, mathematics and bioinformatics in order to find significant difference genes. Methods： With Excel and SPSS software, high or low density chips were analyzed through total intensity normalization （TIN） and locally weighted linear regression normalization （LWLRN）. Results： These methods effectively reduced systemic errors and made data more comparable and reliable. Conclusion： These methods can search the genes of significant difference, although normalization methods are being developed and need to be improved further. Great breakthrough will be obtained in microarray data normalization analysis and transformation with the development of non-linear technology, software and hardware of computer.

Analysis of gene expression profile of aspermia using cDNA microarray

Objective: To identify the differential gene expression profiles between the normal and aspermia human testes utilizing cDNA microarray. Methods: cDNA probes were prepared by labeling mRNA of aspermia testes tissues with Cy5-dUTP and mRNA of normal testes tissues with Cy3-dUTP respectively through reverse transcription. The mixed cDNA probes were then hybridized with 4096 cDNA arrays (4096 unique human cDNA sequences), and the fluorescent signals were scanned by ScanArray 3000 scanner (General Scanning, Inc.). The values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated by ImaGene 3.0 software (BioDiscovery, Inc.). Differentially expressed genes were screened according to the criterion that the absolute value of natural logarithm of the ratio of Cy5-dUTP to Cy3-dUTP was greater-than 2.0 or less-than 0.5. A randomly chosen gene RAP1A was studied by in situ hybridization to evaluate the accuracy of the results. Results: 623 differential expressed genes related to aspermia were found. There were 303 up-expressed genes and 320 down-expressed genes. A distinct up-expressed gene RAP1A was confirmed by in situ hybridization. Conclusions: Screening the differential gene expression profiles between the normal and aspermia human testis by cDNA microarray can be used in the study of aspermia-related genes and the further research due to its properties, RAP1A may play some roles in the development and progression of aspermia.

Analysis of differentially expressed tumor-related genes in Peutz-Jeghers syndrome combined with colorectal carcinoma with cDNA microarrays

Objective:The aim of the study was to screen the differentially expressed genes of Peutz-Jeghers syndrome (PJS) and colorectal carcinoma (CRC).Methods:This study used cDNA microarray to comparatively analyze the gene expression profiles of 4 cases of PJS combined with colorectal adenocarcinoma vs.normal mucosae.The cDNA microarray contained 8064 human genes,and then using RT-PCR to test three genes of all.Results:The experimental data showed that fourteen genes were differentially expressed,which were up-regulated in PJS.Fifty-one genes expressions were altered in CRCs,of which 32 were up-regulated,as compared to the normal mucosae.In addition,5 genes were similarly altered in both PJS and CRCs.RT-PCR analyses confirmed the cDNA microarray data for three of those genes:LATS2,APC and MADH4.Conclusion:LCN2,USP4,GRO3,HYAL1 and APC-these differentially expressed genes likely represent biomarkers for early detection of CRC and may be potential therapeutic targets.

Global gene expression profiles for the growth phases of Trichophyton rubrum

Trichophyton rubrum （T. rubrum） is a common superficial fungus. Molecular and genetic studies of T. rubrum are still limited. In this paper, we report the global analysis of gene expression profiles at different growth phases using cDNA microarray technology. A total of 2044 differentially expressed genes were obtained and clustered into three expression patterns. Our data confirmed previous results that many mRNAs were pre-stored in the conidia of T. rubrum. Transcriptional profiling and function analysis showed that some glycolytic enzymes share similar expression patterns and may be coregulated during the transi- tion of growth phases. Some genes involved in small GTPase signaling pathways, and in cAMP-dependent and MAPK regulation pathways were induced in response to the growth dynamics of T. rubrum. Although the detailed biological roles of these Z rubrum genes are still unknown, our results suggest that these genes may be involved in regulation mechanisms in the life cycle of the fungus.