一个人类睾丸特异表达新基因-septin 12 transcript variant 2的克隆与功能初步研究
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摘要
不育影响着大约10-15%的夫妻,不育的原因夫妻双方约各占一半。遗传因素是男性不育的一个重要因素,男性不育患者染色体检查常常发现有基因缺失、突变或易位。因此生精相关基因的研究对男性不育的诊断和治疗有着重要的意义。精子的发生是一个非常复杂而又受到精确调控的过程,分为有丝分裂阶段、减数分裂阶段和减数分裂后阶段,其中涉及一系列基因的调控,人类的研究表明有2000个以上的基因参与了生精过程,而参与这一过程的蛋白质更多。
随着人类基因组计划(Human Genome Project,HGP)的实施和生物技术的飞速发展,人类基因组测序数据呈指数增长,各种生物数据库及其分析软件相应建立,极大地促进了生物信息学的发展。利用生物信息学克隆新基因和分析基因功能已成为生物信息学研究的热点,大量的新基因被克隆,其中包括不少生精相关基因。本课题尝试利用生物信息学方法寻找新的生精基因,并对其功能进行预测和初步研究,分析该基因在精子生成过程中的作用,有助于进一步了解精子发生的分子机制。
第一章:睾丸特异表达新基因的克隆
精子的生成是一个受多基因调控的过程,目前已发现一系列与精子发生相关的基因,但仍有许多未知基因涉及精子的发生,精子发生与调控的机制仍未阐明。利用生物信息学方法发现新基因是寻找新基因的一条捷径,我们尝试通过数据库消减杂交(DigitalDifferential Display,DDD)方法发现一新的睾丸特异表达基因,并以RT-PCR实验验证。
以因特网UniGene数据库的人类各组织cDNA文库为实验材料,以DDD软件为工具,比较人类睾丸组织和其它组织的cDNA文库,筛选出在睾丸组织中显著高表达并可能代表新基因的的克隆重叠群,将获得的克隆重叠群内的EST(expressed sequence tag)进行同源搜索、拼接和延伸,得到一较长的新基因序列。根据新基因序列设计引物进行PCR反应验证序列拼接是否正确及新基因的真实性。
通过数据库消减杂交(DDD),找到一个在睾丸组织cDNA文库和非睾丸组织cDNA文库中显著差异表达的克隆重叠群Hs.126780,生物信息学分析显示其在睾丸组织中高表达。Hs.126780重叠群包括39条EST,将EST进行拼接、延伸后获得一个新的基因序列,长为1524bp,其中包含一个完整的阅读框架,长1077 bp,编码一358氨基酸的蛋白质,新基因有10个外显子和9个内含子。PCR反应并测序证实新基因序列拼接正确,且在人类睾丸组织中表达。利用生物信息学克隆睾丸特异表达新基因是一种切实可行、高效的新方法,我们运用该方法成功地克隆了一个人类睾丸特异表达新基因,将新基因序列向GenBank数据库提交并被收录,经人类基因命名委员会(Human GeneNomenclature Committee,HGNC)命名为:septin 12 transcriptvariant 2,基因登陆号为:DQ517531。
第二章:新基因及其编码蛋白质的生物信息学分析
在对新基因(septin 12 transcript variant 2)的功能进行研究前我们先利用网络上各种生物学软件,对新基因及其编码的蛋白质进行分析和预测,初步了解新基因的一些特性,为后继的研究提供指导。
利用NCBI的Blast程序对新基因及编码蛋白质进行同源性分析;以BLAST Human Sequences程序进行电子染色体定位;以BioEdit7.0.1软件分析新基因的酶切位点;运用PSORTⅡ软件预测蛋白质细胞内定位;运用ExPASy网站的多个软件对新基因编码蛋白质的理化性质、跨膜区和信号肽序列、疏水性,功能位点进行分析和预测。
生物信息学分析显示新基因与Septin家族多个成员的基因和蛋白质序列有同源性,属于Septin家族基因,该基因无EcoRI、SalI和XhoI酶切位点,基因定位于人类染色体16p13.3,其编码蛋白质的氨基酸序列为358个,分子量为40747D,等电点为6.67。蛋白质细胞内定位:线粒体(可能性为56.5%);胞浆(可能性为17.4%)。无明显跨膜序列和信号肽,推测为非分泌蛋白,有多个磷酸化位点和其它翻译后修饰位点。
第三章:新基因功能的初步研究
基因研究的最终目的是了解其功能,我们进行了多组织RT-PCR(multi-tissue RT-PCR)、Northern印迹杂交(Northern Blots)和原位杂交(in situ hybridization)实验,对新基因的组织表达谱和功能进行了初步研究,并构建了新基因的真核表达载体。
多组织RT-PCR和Northern印迹杂交结果显示新基因在成年男性睾丸组织中高表达,在其它组织中不表达;胎儿除睾丸组织外,在其它少数组织中有微弱表达。新基因在成年睾丸组织中表达最强,在老年睾丸组织中表达减弱,在胎儿睾丸组织中低表达或不表达,在隐睾组织中不表达。新基因在睾丸组织中只表达一个转录本。睾丸组织的原位杂交结果与多组织RT-PCR和Northern印迹杂交结果一致,原位杂交显示新基因主要在精原细胞和精母细胞中表达。
初步研究表明新基因为一睾丸特异表达基因,主要表达于睾丸的精原细胞和精母细胞,其表达与发育阶段有关。新基因的功能可能与精子发生相关,可能参与生精细胞的生长、发育和调亡的调控。
结论:本研究利用生物信息学这一新策略成功克隆了一个人类睾丸特异表达新基因:sept in 12 transcript variant 2,并采用RT-PCR、Northern印迹杂交和原位杂交实验对新基因的表达特征和功能进行初步研究。我们认为新基因在人类精子发生的过程中可能发挥着重要的作用,是一个生精相关基因,具有重要的生理功能。
About 10-15%of couples suffer from infertility,the causes of infertility owe half to male.The hereditary factor plays an important role in infertility of male,gene deletion,mutation or translocation was often observed in infertile patients.The researching of spermatogenesis-related genes is significant to the diagnosis and therapy for male infertility.Spermatogenesis is a very complicated process which is precisely controlled, the process consists of mitosis phase,meiosis phase and postmeiotic phase.Researching indicated that over 2000 genes involve in the process of spermatogenesis,while the proteins involving in the process are much more than the genes.
With the executing of the human genome project(HGP)and the rapid development of biotechnology,the data of human genomic sequence increases enormously,various biology databases are set up,it promotes the development of bioinformatics remarkably.Cloning and functional researching of novel gene by bioinformatics has become the hot spot of biology,many new genes were cloned by this mean,including some spermatogenesis-related genes.We try to discover another new gene related to spermatogenesis by bioinformatics,analyzing it's function, learning the role of it in the process of spermatogenesis,this does some help to reveal the molecular mechanism of spermatogenesis.
PartⅠcloning of a novel testis-specific gene
We compared the testis-derived cDNA libraries and other tissuederived cDNA libraries of human,searching the contig which was expressed in testis much higher than in other tissues,and the contig might represented a new gene,it was chosed for further researching.Assembling and extending the ESTs of the contig by the program BLAST,finaly we obtained a extended sequence,reverse transcription polymerase chain reaction(RT-PCR)was performed to identify the reality of the novel gene and the sequence of open reading frame(ORF).
By the method of Digital Differential Display(DDD),we discovered a contig Hs.126780,which expression was significant different between testis-derived cDNA libraries and other tissue-derived cDNA libraries, bioinformatics analysis indicated it was a testis-specific gene.Hs.126780 consisted of 39 ESTs,assembling the ESTs,a novel elongated homology sequence was obtained,it was 1524bp in length and contained a 1077bp open reading frame(ORF),encoded a protein of 358 amino acid,the new gene consisted of 10 exons.The results of PCR showed that it was really expressed in the testis tissue and the sequence was right.Cloning novel testis-specific gene by bioinformatics was a feasible and high efficient method.We had cloned a novel testis-specific gene by this mean,the new gene was named septin 12 transcript variant 2 by Human Gene Nomenclature(HGNC),and the accession number of GenBank was DQ517531.
PartⅡBioinformatics analysis of the novel gene and protein
we analyzed the new gene and protein of septin 12 transcript variant 2 by bioinformatics before functional researching,this would provide some useful information for late study.Similarlity analysis was performed with the program BLAST.Restriction maps were constructed with the program BioEdit 7.0.1.Comparing with the human genome sketch,we could located the gene in chromosome 16p13.3.Subcellular location was predicted by the software PSORTⅡ.Physico-chemical property,motif searching,transmembrane regions and protein orientation analysis were finished by the tools of ExPASy.Analysis of bioinformatics indicated septin 12 transcript variant 2 belongs to the gene family of septin,it did not have restriction site of EcoR I,SalI and XhoI.The new gene encoded a protein of 358 amino acids with a theoretical molecular weight of 40747D and isoelectric point of 6.67.There were no transmembrane regions,signal peptide and hydrophobie structure in the protein.Several phosphorylation sites and other Post-translational modification sites were found in it.The protein might locate in mitochondria(56.5%)or cytoplasm (17.4%).
PartⅢThe preliminary functional researching of septin 12 transcript variant 2
The ultimate purpose of gene researching was to learn it's function. we had performed preliminary functional researching of the novel gene by methods of multi-tissue RT-PCR,Northern Blots and in situ hybridization. Eukaryotic expression vector pcDNA3.1(+)/septinl 2 and PEGFPC3/septin12 were constructed for late study.All the results displayed that septin 12 transcript variant 2 was a testis-specific gene in adult male,it was expressed in few tissue of fetus,the expression was weak in foetal testis,strongest in adult testis,and down regulated in testis of the aged,and there was no expression in cryptorchidism,only one type of septin 12 transcript was expressed in testis.The results of in situ hybridization displayed the novel gene located in spermatogonium and spermatocyte. Septin 12 transcript variant 2 was a developmental stage-specific and tissue-specific gene,it might concerned with spermatogenesis and probably involved in division,development and apoptosis of germ cell.
Conclusion:We had cloned a testis-specific gene septin 12 transcript variant 2 successfully.Multi-tissue RT-PCR,Northern Blots and in situ hybridization were used to research the expression character and function of it,all the results demonstrated that septin 12 transcript variant 2 might be a spermatogenesis-related gene,and play an important role in spermatogenesis.
随着人类基因组计划(Human Genome Project,HGP)的实施和生物技术的飞速发展,人类基因组测序数据呈指数增长,各种生物数据库及其分析软件相应建立,极大地促进了生物信息学的发展。利用生物信息学克隆新基因和分析基因功能已成为生物信息学研究的热点,大量的新基因被克隆,其中包括不少生精相关基因。本课题尝试利用生物信息学方法寻找新的生精基因,并对其功能进行预测和初步研究,分析该基因在精子生成过程中的作用,有助于进一步了解精子发生的分子机制。
第一章:睾丸特异表达新基因的克隆
精子的生成是一个受多基因调控的过程,目前已发现一系列与精子发生相关的基因,但仍有许多未知基因涉及精子的发生,精子发生与调控的机制仍未阐明。利用生物信息学方法发现新基因是寻找新基因的一条捷径,我们尝试通过数据库消减杂交(DigitalDifferential Display,DDD)方法发现一新的睾丸特异表达基因,并以RT-PCR实验验证。
以因特网UniGene数据库的人类各组织cDNA文库为实验材料,以DDD软件为工具,比较人类睾丸组织和其它组织的cDNA文库,筛选出在睾丸组织中显著高表达并可能代表新基因的的克隆重叠群,将获得的克隆重叠群内的EST(expressed sequence tag)进行同源搜索、拼接和延伸,得到一较长的新基因序列。根据新基因序列设计引物进行PCR反应验证序列拼接是否正确及新基因的真实性。
通过数据库消减杂交(DDD),找到一个在睾丸组织cDNA文库和非睾丸组织cDNA文库中显著差异表达的克隆重叠群Hs.126780,生物信息学分析显示其在睾丸组织中高表达。Hs.126780重叠群包括39条EST,将EST进行拼接、延伸后获得一个新的基因序列,长为1524bp,其中包含一个完整的阅读框架,长1077 bp,编码一358氨基酸的蛋白质,新基因有10个外显子和9个内含子。PCR反应并测序证实新基因序列拼接正确,且在人类睾丸组织中表达。利用生物信息学克隆睾丸特异表达新基因是一种切实可行、高效的新方法,我们运用该方法成功地克隆了一个人类睾丸特异表达新基因,将新基因序列向GenBank数据库提交并被收录,经人类基因命名委员会(Human GeneNomenclature Committee,HGNC)命名为:septin 12 transcriptvariant 2,基因登陆号为:DQ517531。
第二章:新基因及其编码蛋白质的生物信息学分析
在对新基因(septin 12 transcript variant 2)的功能进行研究前我们先利用网络上各种生物学软件,对新基因及其编码的蛋白质进行分析和预测,初步了解新基因的一些特性,为后继的研究提供指导。
利用NCBI的Blast程序对新基因及编码蛋白质进行同源性分析;以BLAST Human Sequences程序进行电子染色体定位;以BioEdit7.0.1软件分析新基因的酶切位点;运用PSORTⅡ软件预测蛋白质细胞内定位;运用ExPASy网站的多个软件对新基因编码蛋白质的理化性质、跨膜区和信号肽序列、疏水性,功能位点进行分析和预测。
生物信息学分析显示新基因与Septin家族多个成员的基因和蛋白质序列有同源性,属于Septin家族基因,该基因无EcoRI、SalI和XhoI酶切位点,基因定位于人类染色体16p13.3,其编码蛋白质的氨基酸序列为358个,分子量为40747D,等电点为6.67。蛋白质细胞内定位:线粒体(可能性为56.5%);胞浆(可能性为17.4%)。无明显跨膜序列和信号肽,推测为非分泌蛋白,有多个磷酸化位点和其它翻译后修饰位点。
第三章:新基因功能的初步研究
基因研究的最终目的是了解其功能,我们进行了多组织RT-PCR(multi-tissue RT-PCR)、Northern印迹杂交(Northern Blots)和原位杂交(in situ hybridization)实验,对新基因的组织表达谱和功能进行了初步研究,并构建了新基因的真核表达载体。
多组织RT-PCR和Northern印迹杂交结果显示新基因在成年男性睾丸组织中高表达,在其它组织中不表达;胎儿除睾丸组织外,在其它少数组织中有微弱表达。新基因在成年睾丸组织中表达最强,在老年睾丸组织中表达减弱,在胎儿睾丸组织中低表达或不表达,在隐睾组织中不表达。新基因在睾丸组织中只表达一个转录本。睾丸组织的原位杂交结果与多组织RT-PCR和Northern印迹杂交结果一致,原位杂交显示新基因主要在精原细胞和精母细胞中表达。
初步研究表明新基因为一睾丸特异表达基因,主要表达于睾丸的精原细胞和精母细胞,其表达与发育阶段有关。新基因的功能可能与精子发生相关,可能参与生精细胞的生长、发育和调亡的调控。
结论:本研究利用生物信息学这一新策略成功克隆了一个人类睾丸特异表达新基因:sept in 12 transcript variant 2,并采用RT-PCR、Northern印迹杂交和原位杂交实验对新基因的表达特征和功能进行初步研究。我们认为新基因在人类精子发生的过程中可能发挥着重要的作用,是一个生精相关基因,具有重要的生理功能。
About 10-15%of couples suffer from infertility,the causes of infertility owe half to male.The hereditary factor plays an important role in infertility of male,gene deletion,mutation or translocation was often observed in infertile patients.The researching of spermatogenesis-related genes is significant to the diagnosis and therapy for male infertility.Spermatogenesis is a very complicated process which is precisely controlled, the process consists of mitosis phase,meiosis phase and postmeiotic phase.Researching indicated that over 2000 genes involve in the process of spermatogenesis,while the proteins involving in the process are much more than the genes.
With the executing of the human genome project(HGP)and the rapid development of biotechnology,the data of human genomic sequence increases enormously,various biology databases are set up,it promotes the development of bioinformatics remarkably.Cloning and functional researching of novel gene by bioinformatics has become the hot spot of biology,many new genes were cloned by this mean,including some spermatogenesis-related genes.We try to discover another new gene related to spermatogenesis by bioinformatics,analyzing it's function, learning the role of it in the process of spermatogenesis,this does some help to reveal the molecular mechanism of spermatogenesis.
PartⅠcloning of a novel testis-specific gene
We compared the testis-derived cDNA libraries and other tissuederived cDNA libraries of human,searching the contig which was expressed in testis much higher than in other tissues,and the contig might represented a new gene,it was chosed for further researching.Assembling and extending the ESTs of the contig by the program BLAST,finaly we obtained a extended sequence,reverse transcription polymerase chain reaction(RT-PCR)was performed to identify the reality of the novel gene and the sequence of open reading frame(ORF).
By the method of Digital Differential Display(DDD),we discovered a contig Hs.126780,which expression was significant different between testis-derived cDNA libraries and other tissue-derived cDNA libraries, bioinformatics analysis indicated it was a testis-specific gene.Hs.126780 consisted of 39 ESTs,assembling the ESTs,a novel elongated homology sequence was obtained,it was 1524bp in length and contained a 1077bp open reading frame(ORF),encoded a protein of 358 amino acid,the new gene consisted of 10 exons.The results of PCR showed that it was really expressed in the testis tissue and the sequence was right.Cloning novel testis-specific gene by bioinformatics was a feasible and high efficient method.We had cloned a novel testis-specific gene by this mean,the new gene was named septin 12 transcript variant 2 by Human Gene Nomenclature(HGNC),and the accession number of GenBank was DQ517531.
PartⅡBioinformatics analysis of the novel gene and protein
we analyzed the new gene and protein of septin 12 transcript variant 2 by bioinformatics before functional researching,this would provide some useful information for late study.Similarlity analysis was performed with the program BLAST.Restriction maps were constructed with the program BioEdit 7.0.1.Comparing with the human genome sketch,we could located the gene in chromosome 16p13.3.Subcellular location was predicted by the software PSORTⅡ.Physico-chemical property,motif searching,transmembrane regions and protein orientation analysis were finished by the tools of ExPASy.Analysis of bioinformatics indicated septin 12 transcript variant 2 belongs to the gene family of septin,it did not have restriction site of EcoR I,SalI and XhoI.The new gene encoded a protein of 358 amino acids with a theoretical molecular weight of 40747D and isoelectric point of 6.67.There were no transmembrane regions,signal peptide and hydrophobie structure in the protein.Several phosphorylation sites and other Post-translational modification sites were found in it.The protein might locate in mitochondria(56.5%)or cytoplasm (17.4%).
PartⅢThe preliminary functional researching of septin 12 transcript variant 2
The ultimate purpose of gene researching was to learn it's function. we had performed preliminary functional researching of the novel gene by methods of multi-tissue RT-PCR,Northern Blots and in situ hybridization. Eukaryotic expression vector pcDNA3.1(+)/septinl 2 and PEGFPC3/septin12 were constructed for late study.All the results displayed that septin 12 transcript variant 2 was a testis-specific gene in adult male,it was expressed in few tissue of fetus,the expression was weak in foetal testis,strongest in adult testis,and down regulated in testis of the aged,and there was no expression in cryptorchidism,only one type of septin 12 transcript was expressed in testis.The results of in situ hybridization displayed the novel gene located in spermatogonium and spermatocyte. Septin 12 transcript variant 2 was a developmental stage-specific and tissue-specific gene,it might concerned with spermatogenesis and probably involved in division,development and apoptosis of germ cell.
Conclusion:We had cloned a testis-specific gene septin 12 transcript variant 2 successfully.Multi-tissue RT-PCR,Northern Blots and in situ hybridization were used to research the expression character and function of it,all the results demonstrated that septin 12 transcript variant 2 might be a spermatogenesis-related gene,and play an important role in spermatogenesis.
引文
[1]Rice E.The Human Genome Project and gene therapy:a genetic counse- lor's perspective.J Perinat Neonatal Nurs,1998,12(3):16-25.
[2]Ikekawa A,Ikekawa S.Fruits of human genome project and private venture,and their impact on life science.Yakugaku Zasshi,2001,121(12):845-873.
[3]Freeman K.Harnessing the HGP of public health.Environ Health Perspect,2004,112(7):A402.
[4]Luscombe NM,Greenbaum D,Gerstein M.What is bioinformatics? A proposed definition and overview of the field.Methods Inf Med,2001,40(4):346-358.
[5]Burkle T,Hain T,Hossain H,et al.Bioinformatics in medical practice:what is necessary for a hospital? Medinfo,2001,10(Pt2):951-955.
[6]Ashida H.What is bioinformatics?Rinsho Byori,2002,50(1):40-44.
[7]Qiang Lu,Pei Hao,Vasa Curcin,et al.KDE Bioscience:Platform for bioinformatics analysis workflows.Journal of Biomedical informatics,2006,39(4):440-450.
[8]王发生,毛君莲.生命科学时代的生物信息学.中国现代医学杂志,2000,10(12):108-109.
[9]Liebman MN.Biomedical informatics:the future for drug development.Drug Discov Today,2002,7(20 Suppl):S197-203.
[10]Wishart.Bioinformatics in drug development and assessment.Drug Metab Rev,2005,37(2):279-310.
[11]Volker C,Brown JR.Bioinformatics and the discovery of novel antimic-robial targets.Curr DrugTargets Infect Disord,2002,2(4):279-290.
[12]McCarthy FM,Wang N,Magee GB,et al.AgBase:a functional genomics resource for agriculture.BMC Genomics,2006,7:229
[13]Rhee SY,Dickerson J,Xu D.Bioinformatics and its applications in plant biology.Annu Rev Plant Bioi,2006,57:335-360.
[14]Li D,Lu GX,Fu JJ,et al.Molecular cloning and expression analysis of a novel human testis-Spcificgene.Yi Chuan Xue Bao,2004,31(6)545-551.
[15]Nie DS,Zhu WB,Xiang Y.Molecular cloning and primary functional analy-sis of a novel human testis-specific gene.Yi Chuan Xue Bao,2005,32(4):337-345.
[16]Li D,Lu GX.Identification and expression of a novel human testis-specific gene by digital differential display.Chin Med J(Engl),2004,117(12):1791-1796.
[17]Fu JJ,Lu GX,Li LY,et al.Molecular cloning for testis spermatogenesis cell apoptosis related gene TSARG1 and Mtsargl and expression analysis for Mtsargl gene.Yi Chuan Xue Bao,2003,30(1):25-29.
[18]Nie DS,Xiang Y,Wang J.Identification of a novel testis-specific gene mtLR1,which is expressed at specific stages of mouse spermatogenesis.Biochem Biophys Res Commun,2005,328(4):1010-1018.
[19]Benagiano G,Bastianelli C,Farris M.Infertility:a global perspective.Minerva Ginecol,2006,58(6):445-457
[20]Illions EH.Infertility:etiologies,evaluation and treatments.Drugs Today (Bare),2000,36(6):369-382.
[21]Krausz C,Degl'Innocenti S.Y chromosome and male infertility:update,2006.Front Biosci,2006,11:3049-3061.
[22]Aitken RJ,Skakkebaek NE,Roman SD.Male reproductive health and the environment.Med J Aust,2006,185(8):414-415.
[23]Sallmen M,Sandier DP,Hoppin JA,et al.Reduced fertility among overweight and obese men.Epidemiology,2006,17(5):520-523.
[24]Said TM,Ranga G,Agarwal A.Relationship between semen quality and tobacco chewing in men undergoing infertility evaluation.Fertil Steril,2005,84(3):649-653.
[25]Lenzi A,Lombardo F,Salacone P.et.al.Stress,sexual dysfunctions,and male infertility.J Endoerinol Invest,2003,26(3 Suppl):72-76.
[26]Trokoudes KM,Skordis N,Picolos MK.Infertility and thyroid disorders.Curr Opin Obstet Gynecol,2006,18(4):446-451.
[27]Engel W,Adham IM.Nayemia K.et al.Genetic causes of male infertility.Verb Dtsch Ges Pathol,2004,88:130-135.
[28]Ferlin A,Arredi B,Foresta C.Genetic causes of male infertility.Reprod Toxicol,2006,22(2):133-141.
[29]Lilford R,Jones AM,Bishop DT,et al.Case-control study of whether subfertility in men is familial.BMJ,1994,309(6954):570-573.
[30]Ekerhovd E.Infertility treatment of men with azoospermia.Tidsskr Nor Laegeforen,2006,126(12):1598-1601.
[31]Tiepolo L,Zuffardi O.Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm.Hum Genet,1976,34(2):119-124.
[32]Reijo R,Lee TY,Salo P,et al.Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene.Nat Genet,1995,10(4):383-393.
[33]邵敏杰,张颖.特发性无精子症少精子症患者分子遗传学及血清学的研究进展.中国优生与遗传杂志,2005,13(7):12-14.
[34]Kent-First M,Muallem A,Shultz J,et al.Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region(AZFd)by Y-chromosome microdeletion detection.Mol Reprod Dev,1999,53(1):27-41.
[35]崔英霞,王咏梅,徐建平,等.与精子发生障碍相关的染色体畸变.中华男科学,2001,7(2):99-101.
[36]Huminiecki L,Bicknell R.In silico cloning of novel endothelial-specific genes.GenomeRes,2000,10(11):1796-1806.
[37]Huang J,Wang JF,Zhang HS,et al.In silico cloning of glucose -6- phosphate dehydrogenase eDNA from rice(Oryza sativa L).Yi Chuan Xue Bao,2002,29(11):1012-1016.
[38]张成岗,贺福初.生物信息学方法与实践.北京:科学出版社,2002.16-17.
[39]Sun CX,Yu AC.A brief introduction to the methods for novel gene cloning.Sheng Li Ke Xue Jin Zhan,2000,31(1):35-42.
[40]Huang W,Fang XD,Zhao WM,et al.The methods of identifying differences in mRNA expression.Sheng Wu Gong Cheng Xue Bao,2002,18(4):521-524.
[41]Liang P,Pardee AB.Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction.Science,1992,257(5072):67-971.
[42]Velculescu VE,Zhang L,Vogelstein B,et al.Serial analysis of gene expression.Science,1995,270(5235):484-487.
[43]潘泽民,潘晓琳,杨磊,等.基因表达系列分析(SAGE)技术在肿瘤研究中的应用.生命的化学,2004,24(4):322-324.
[44]Diatchenko L,Lau YF,Campbell AP,et al.Suppression subtractive hybridization:a method for generating differentially regulated or tissue-specific cDNA probes and libraries.Proc Natl Acad Sci U S A,1996,93(12):6025-6030.
[45]杨春梅,万柏坤,梁慧嫒,等.DNA微阵列技术及其在生物医学中的应用.国外医学生物医学工程分册,2002,25(5)203-206.
[46]Liu SF,Li LY,Fu JJ,et al.Rapid identification of human testis spermatocyte apoptosis-related gene,TSARG2,by nested PCR and draft human genome searching,Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao, 2002,34(3):378-382.
[47]Liu G,Lu G,Fu J,et al.Molecular cloning of TSARG3 gene related to apoptosis in human spermatogenic cells,Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2003,20(2):107-110.
[48]Xing XW,Li LY,Fu JJ,et al.Cloning of eDNA of TSARG4,a human spermatogenesis related gene,Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao,2003,35(3):283-288.
[49]Zneimer SM.The human genome project:exploring its progress and successes and the ethical,legal,and social implications.Clin Leadersh Manag Rev,2002,16(3):151-157.
[50]Trent RJ.Milestones in the Human Genome Project:genesis to postgenome,Med J Aust,2000,173(11-12):591-594.
[51]Kulikova T,Aldebert P,Althorpe N.The EMBL Nueleotide Sequence Database.Nucleic Acids Res,2004,32(Database issue):D27-30.
[52]Johnson RS,Davis MT,Taylor JA.Informatics for protein identification by mass spectrometry.Methods,2005,35(3):223-236.
[53]Agarwal P,States DJ.Comparative accuracy of methods for protein sequence similarity search.Bioinformatics,1998,14(1):40-47.
[54]Webber C,Barton GJ.Increased coverage obtained by combination of methods for protein sequence database searching.Bioinformatics,2003,19(11):1397-1403.
[55]Contreras CF,Canales MA,Alvarez A.Molecular modeling of the amyloid-beta-peptide using the homology to a fragment of triosephosphate iso- merase that forms amyloid in vitro.Protein Eng,1999,12(11):959-966.
[56]江荣才,于士柱,浦佩玉,等.应用微阵列技术初步探讨间变性星形细胞瘤基因表达谱.中华病理学杂志,2004,33(4):371-372.
[57]江荣才,浦佩玉,焦保华,等.CDC10在胶质瘤中的表达.中国临床神经科学,2002,10(3):227-229.
[58]Rotmistrovsky K,Jang W,Schuler GD.A web server for performing electronic PCR.Nucleic Acids Res,2004,32(Web Server issue):W108-12.
[59]Martin J,Han C,Gordon LA,et al.The sequence and analysis of duplication-rich human chromosome 16.Nature,2004,432(7020):988-994.
[60]Takeuchi A,Mishina Y,Miyaishi O,et al.Heterozygosity with respect to Zfp148causes complete loss of fetal germ cells during mouse embryogenesis.Nat Genet,2003,33(2):172-176.
[61]Rovio AT,Marchington DR,Donat S,et al.Mutations at the mitochon- drial DNA polymerase(POLG)locus associated with male infertility.Nat Genet,2001,29(3):261-262.
[62]Sigrist CJ,Cerutti L,Hulo N,et al.PROSITE:a documented database using patterns and profiles as motif descriptors.Brief Bioinform,2002,3(3):265-274.
[63]Hulo N,Bairoch A,Bulliard V,et al.The PROSITE database.Nucleic Acids Res,2006,34(Data base issue):D227-230.
[64]Hu H,Yu WB,Li SX,et al.Crystallization and preliminary crystal-lographic studies of human septin 1 with site-directed mutations.Acta Crystallograph Sect F Struct Biol Cryst Commun,2006,62(Pt2):128-132.
[65]Huang YW,Surka MC,Reynaud D,et al.GTP binding and hydrolysis kinetics of human septin 2.FEBS J,2006,273(14):3248-3260.
[66]Douglas LM,Alvarez FJ,McCreary C,et al.Septin function in yeast model systems and pathogenic fungi.Eukaryot Cell,2005,4(9):1503-1512.
[67]Low C,Macara IG.Structural analysis of septin 2,6,and 7 comp- lexesJ Biol Chem,2006,281(41):30697-30706.
[68]Hall PA,Jung K,Hillan KJ,et al.Expression profiling the human septin gene family.J Pathol,2005,206(3):269-278.
[69]Martinez C,Ware J.Mammalian septin function in hemostasis and beyond.Exp Biol Med(Maywood),2004,229(11):1111-1119.
[70]Ono R,Ihara M,Nakajima H,et al.Disruption of Sept6,a fusion partner gene of MLL,does not affect ontogeny,leukemogenesis induced by MLL-SEPT6,or phenotype induced by the loss of Sept4.Mol Cell Biol,2005,25(24):10965-10978.
[71]Hall PA,Russell SE.The pathobiology of the septin gene family.J Pathol,2004,204(4):489-505.
[72]Kinoshita M.Assembly of mammalian septins.J Biochem(Tokyo),2003,134(4):491-496.
[73]Kremer BE,Haystead T,Macara IG.Mammalian septins regulate microtubule stability through interaction with the microtubule- binding protein MAP4.Mol Biol Cell,2005,16(10):4648-4659.
[74]Gladfelter AS,Zyla TR,Lew DJ.Genetic interactions among regulators of septin organization.Eukaryot Cell,2004,3(4):847-854.
[75]Craven RA,Hanrahan S,Totty N,et al.Proteomic identification of a role for the von Hippel Lindau tumour suppressor in changes in the expression of mitochondrial proteins and septin 2 in renal cell carcinoma.Proteomics,2006,6(13):3880-3893.
[76]Kim DS,Hubbard SL,Peraud A,et al Analysis of mammalian septin expression in human malignant brain tumors.Neoplasia,2004,6(2):168-78.
[77]Scott M,McCluggage WG,Hillan KJ,et al.Altered patterns of transcription of the septin gene,SEPT9,in ovarian tumorigenesis.Int J Cancer,2006,118(5):1325-1329.
[78]Kalikin LM,Sims HL,Petty EM.Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene(MSF)that map to a 17q25 region of loss in breast and ovarian tumors.Genomics,2000,63(2):165-172.
[79]Cerveim N,Correia C,Bizarro S,et al.SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23).Oncogene,2006,25(45):6147-6152.
[80]Gonzalez-Novo A,Jimenez J,Garcia MJ,et al.Dynamics of CaCdc10,a septin of Candida albieans,in living cells and during infecfion.Int Microbiol,2004,7(2):105-112.
[81]Takehashi M,Tanaka S,Stedeford T,et al.Expression of septin 3 isoforms in human brain.Gene Expr,2004,1(5-6):271-278.
[82]Kuhlenbaumer G,Hannibal MC,Nelis E,et al.Mutations in SEPT9 cause hereditary neuralgic amyotrophy.Nat Genet,2005,37(10):1044-1046.
[83]Kissel H,Georgescu MM,Larisch S,,et al.The Sept4 septin locus is required for sperm terminal differentiation in mice.Dev Cell,2005,8(3):353-364.
[84]Ihara M,Kinoshita A,Yamada S,et al.Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa.Dev Cell,2005,8(3):343-352.
[85]Lin YM,Teng YN,Lee PC,et al.AZFa candidate gene deletions in Taiwanese patients with spermatogenic failure.J Formos Med Assoc,2001,100(9):592-597.
[86]Krausz C,McElreavey K.Y chromosome and male infertility.Front Biosci,1999,4:E1-8.
[87]Fujisawa M,Shirakawa T,Kanzaki M,et al.Y-chromosome mierodeletion and phenotype in cytogenetically normal men with idiopathic azoospermia.Fertil Steril,2001,76(3):491-495.
[88]Taskiran C,Baltaci V,Gunalp S.Globozoospermia:Do Y-chromosome microdeletions play a role in this rare spermatogenic disorder?J Reprod Med,2006,1(8):628-634.
[89]Shafik A,Shafik AA,Shafik I,et al.ular andrology as related to sperm DNA fragmentation/sperm chromatin biotechnology.Arch Androl,2006,52(4):299-310.
[90]Melo KF,Mendonca BB,Billerbeck AE,et al.Androgen insensitivity syndrome:clinical,hormonal and molecular analysis of 33 cases.Arq Bras Endocrinol Metabol,2005,49(1):87-97.
[91]Seligman J,Page DC.The Dazh gene is expressed in male and female embryonic gonads before germ cell sex differentiation.Biochem Bio- phys Res Commun,1998,245(3):878-882.
[92]Yen PH,Chai NN,Salido EC.The human autosomal gene DAZLA:testis specificity and a candidate for male infertility.Hum Mol Genet,1996,5(12):2013-2017.
[93]Krausz C,Sassone-Corsi P.Genetic control of spermiogenesis:insi- ghts from the CREM gene and implications for human infertility.Reprod Biomed Online,2005,10(1):64-71.
[94]Blocher S,Fink L,Bohle RM,et al CREM activator and repressor isoform expression in human male germ cells.Int J Androl,2005,28(4):215-223.
[95]Dix DJ,Allen JW,Collins BW,et al.Targeted gene disruption of Hsp70-2 results in failed meiosis,germ cell apoptosis,and male infertility.Proc Natl Acad Sci U S A,1996,93(8):3264-3268.
[96]Zhu D,Dix DJ,Eddy EM.HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes.Development,1997,124(15):3007-3014.
[97]Aarabi M,Modarressi MH,Soltanghoraee H,et al.Testicular expre- ssion of synaptonemal complex protein 3(SYCP3)messenger ribonu- cleic acid in 110patients with nonobstructive azoospermia.Fertil Steril,2006,86(2):325-331.
[98]Miyamoto T,Hasuike S,Yogev L,et al.Azoospermia in patients heterozygous for a mutation in SYCP3.Lancet,2003,362(9397):1714-1719.
[99]Grimaldi P,Rossi P,Dolci S,et al.Molecular genetics of male infertility:stem cell factor/c-kit system.Am J Reprod Immunol,2002,48(1):27-33.
[100]宋宁宏,苏建堂.基因缺陷对精子发生的影响.国外医学,2003,23(2):176-179.
[1] Qiang Lu, Pei Hao, Vasa Curcin,et al.KDE Bioscience: Platform for bioin-formatics analysis workflows. Journal of Biomedical informatics , 2006, 39(4): 440-450.
[2] Liebman MN. Biomedical informatics: the future for drug development. Drug Discov Today, 2002 ,7(20 Suppl):S197-203.
[3] Wishart.Bioinformatics in drug development and assessment.Drug Metab Rev, 2005,37(2):279-310.
[4] Volker C,Brown JR.Bioinformatics and the discovery of novel anti-microbial targets. Curr Drug Targets Infect Disord,2002 ,2(4):279-290.
[5] McCarthy FM, Wang N, Magee GB, et al.AgBase: a functional genomics resource for agriculture. BMC Genomics,2006,7:229.
[6] Rhee SY,Dickerson J,Xu D. Bioinformatics and Its Applications in Plant Biology. Annu Rev Plant Biol,2005 ,[Epub ahead of print].
[7] Rajpal DK. Understanding biology through bioinformatics.Int J Toxicol, 2005, 24(3):147-152.
[8] Janet M.Thornton.Trends Guide To Bioinformatics,30-31.
[9] Benson DA,Karsch-Mizrachi,Lipman DJ, et al. GenBank. Nucleic Acids Res 2006,34(Database issue):D16-20.
[10]Letovsky SI,Cottingham RW,Porter CJ,et.al. GDB: the Human Genome Database. Nucleic Acids Res, 1998 ,26(1):94-9.
[11]Cuticchia AJ. Future vision of the GDB human genome database. Hum Mutat, 2000,15(1):62-67.
[12]Rabhan M,Chalifa-Caspi V,Prilusky J, et al. GeneCards: integrating information about genes, proteins and diseases.Trends Genet, 1997,13(4):163.
[13] White O,Kerlavage AR. TDB: new databases for biological discovery. Methods Enzymol, 1996,266:27-40.
[14] Wheeler DL,Barrett T,Benson DA,et al. Database resources of the National Center for Biotech- nology Information.Nucleic Acids Res, 2006,34(Database issue):D173-180.
[15]Apweiler R,Bairoch A,Wu CH.Protein sequence databases. Curr Opin Chem Biol,2004,8(1):76-80.
[16]Boeckmann B,Bairoch A,Apweiler R,et al.The SWISS-PROT protein knowle- dgebase and its supplement TrEMBL in 2003.Nucleic Acids Res,2003,31(1):365-370.
[17]Boeckmann B,Bairoch A,Apweiler R,et al.The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003,Nucleic Acids Res,31(1):365-370.
[18]Schneider M,Tognolli M,Bairoch A,et al.The Swiss-Prot protein knowledgebase and ExPASy:providing the plant community with high quality proteomic data and tools.Plant Physiol Biochem,2004,42(12):1013-1021.
[19]Apweiler R,Bairch A,Wu CH,et al.UniProt:the Universal Protein knowle-dgebase.Nucleic Acids Res,2004,32(Database issue):D115-119.
[20]Bairch A,Apweiler R,Wu CH,et al.The Universal Protein Resource(UniProt).Nucleic Acids Res,2005,33:D154-159.
[21]O'Donovan C,Martin MJ,Gattiker,et al.High-quality protein knowledge resource:SWISS-PROT and TrEMBL.Bdef Bioinform,2002,3(3):275-284.
[22]Berman HM,Battistuz T,Bhat TN,et al.The Protein Data Bank.,Acta Crystallogr D Biol Crystallogr,2002,58(Pt 6 No 1):899-907.
[23]Andreeva A,Howorth D,Brermer SE,et al.SCOP database in 2004:refinements integrate structure and sequence family data.Nucleic Acids Res,2004,32(Database issue):D226-229.
[24]Ison JC.Exploring protein domain structure..Bdef Bioinform,2000,1(3):305-312.
[25]Stoesser G,Baker W,Vab den Broek A,et al.The EMBL nucleotide sequence database.Nucleic Acids Res,2001,29(1):17-21.
[26]Geer RC,Sayers EW.Entrez:making use of its power.Brief Bioinform,2003,4(2):179-184.
[27]张成岗,贺福初.生物信息学方法与实践.北京:科学出版社,2002:16-17.
[28]To KY.Identification of differential gene expression by high throughput analysis.Comb Chem High Throughput Screen,2000,3(3):235-241.
[29]Li D,Lu GX,Fu JJ,et al.Molecular cloning and expression analysis of a novel human testis-Spcific gene.Yi Chuan Xue Bao,2004,31(6):545-551.
[30]Nie DS,Zhu WB,Xiang Y.Molecular cloning and primary functional analysis of a novel human testis-specific gene.Yi Chuan Xue Bao,2005,32(4):337-345.
[31]LiD,Lu GX.Identification and expression of a novel human testis-specific gene by digital diferenfial display.Chi n Med J(Engl),2004,117(12):1791-1796.
[32]Fu JJ,Lu GX,Li LY,et al.Molecular cloning for testis spermatogenesis cell apoptosis related gene TSARG1 and Mtsargl and expression analysis for Mtsargl gene. Yi Chuan Xue Bao,2003,30(1):25-29.
[33]Nie DS,Xiang Y,Wang J. Identification of a novel testis-specific gene mtLR1, which is expressed at specific stages of mouse spermatogenesis.Biochem Biophys Res Commun, 2005 ,328(4):1010-1018.
[34]Scheurle D,DeYoung MP,Binninger DM, , et al. Cancer gene discovery using digital differential display.Cancer Res, 2000 ,60(15):4037-4043.
[35]Schaefer C,Grouse L,Buetow K,et al.A new cancer genome anatomy project web resourse for the Community,Cancer J,2001,7(1):52-60.
[36]Strausberg RL.The Cancer Genome Anatomy Project:new resources for reading the molecular signatures of cancer.J Pathol,2001,195(1):31-40.
[37]Schaefer C,Grouse L,Buetow K. A new cancer genome anatomy project web resource for the community.Cancer J, 2001,7(1):52-60.
[38]Riggins GJ. Using Serial Analysis of Gene Expression to identify tumor markers and antigens. Dis Markers, 2001,17(2) :41-48.
[39]De Young MP,Damania H,Scheurle D.bioinformatics-Based discovery of a novel factor with apparent specificity to colon cancer,2002,16(4):239-248.
[40] Stekel DJ,Git Y, Falciani F, The comparison of gene expression from multiple cDNA libraries.Genome Res, 2000,10(12):2055-2061.
[41]Kulikova T,Aldebert P,Althorpe N. The EMBL Nucleotide Sequence Database.Nucleic Acids Res, 2004,32(Database issue):D27-30.
[42] Johnson RS, Davis MT, Taylor JA. Informatics for protein identification by mass spectrometry. Methods, 2005,35(3):223-236.
[43]Agarwal P,States DJ. Comparative accuracy of methods for protein sequence similarity search. Bioinformatics, 1998;14(1):40-47.
[44] Chen TG,Wu SF,Wan P.Gene prediction and function research of SARS-CoV(BJ01). Yi Chuan Xue Bao,2003,30(8):773-780.
[45]Agarwal P,States DJ. Comparative accuracy of methods for protein sequence similarity search. Bioinformatics, 1998,14(1):40-47.
[46]Contreras CF, Canales MA, Alvarez A.Molecular modeling of the amyloid-beta-peptide using the homology to a fragment of triosephosphate isomerase that forms amyloid in vitro. Protein Eng, 1999 ,12(11):959-966.
[47] Burke J,Davison,Hide W. d2_cluster: a validated method for clustering EST and full-length cDNAsequences.Genome Res, 1999,9(11):1135-1142.
[48]Rotmistrovsky K,Jang W,Schuler GD.A web server for performing electronic PCR.Nucleic Acids Res,2004,32(Web Server issue):W108-12.
[49]Wheeler DL,Church DM,Federhen S.Database resources of the National Center for Biotechnology.Nucleic Acids Res,2003,31(1):28-33.
[50]Guigo R,Agarwal P,Abril JF.An assessment of gene prediction accuracy in large DNA sequences.Genome Res,2000,10(10):1631-1642.
[51]Burge C,Karlin S.Prediction of complete gene structures in human genomic DNA.J Mol Biol,1997,268(1):78-94.
[52]Schmid CD,Perier R,Praz V,et al.EPD in its twentieth year:towards complete promoter coverage of selected model organisms.Nucleic Acids Res,2006,34(Database issue):D82-85.
[53]Wingender E.TRANSFAC,TRANSPATH and CYTOMER as starting points for an ontology of regulatory networks.In Silico Biol,2004;4(1):55-61.
[54]Fogel GB,Weekes DG,Varga G,et al.A statistical analysis of the TRANSFAC database.Biosystems,2005,81(2):137-154.
[55]Pesole G,Liuni S,D'Souza M.PatSearch:a pattern matcher software that finds functional elements in nucleotide and protein sequences and assesses their statistical significance.Bioinformatics,2000,16(5):439-450.
[56]Grillo G,Licciulli F,Liuni S,PatSearch:A program for the detection of patterns and structural motifs in nucleotide sequences.Nucleic Acids Res,2003,31(13):3608-3612.
[57]Wishart DS,Fortin S.The BioTools Suite.A comprehensive suite of latform-independent bioinformatics tools.Mol Biotechnol,2001,19(1):59-77.
[58]Wishart DS,Stothard P,Van Domselaar GH.PepTool and GeneTool:platform-independent tools for biological sequence analysis.Methods Mol Biol,2000,132:93-113.
[59]Lu G,Moriyama EN.Vector NTI,a balanced all-in-one sequence analysis suite.Brief Bioinform,2004,5(4):378-388.
[60]Ikeda M,Arai M,Lao DM,et al.Transmembrane topology prediction methods:a re-assessment and improvement by a consensus method using a dataset of experimentally-characterized transmembra- ne topologies.In Silico Biol,2002,2(1):19-33.
[61]Bertaccini E,Trudell JR.Predicting the transmembrane secondary structure of ligand-gated ion channels.Protein Eng,2002,15(6):443-454.
[62]Tusnady GE, Simon I. The HMMTOP transmembrane topology prediction server.Bioinformatics, 2001,17(9):849-850.
[63]Rost B, Yachdav G, Liu J. The PredictProtein server.Nucleic Acids Res, 2004,32(Web Server issue):W321-326.
[64]Emanuelsson O, Nielsen H, Brunak S. Predicting subcellular localization of proteins based on their N-terminal amino acid sequence.J Mol Biol, 2000 , 300(4):1005-1016.
[65]Berjanskii MV, Neal S, Wishart DS. PREDITOR: a web server for predicting protein torsion angle restraints.Nucleic Acids Res, 2006 ,34(Web Server issue): W63-69.
[66] Zhang CT, Zhang R. A graphic approach to evaluate algorithms of secondary structure prediction. J Biomol Struct Dyn, 2000,17(5):829-842.
[67]Rost B, Liu J. The PredictProtein server.Nucleic Acids Res, 2003,31 (13):3300-3304.
[68] Arnold K, Bordoli L, Kopp J, et al.The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling.Bioinformatics, 2006 ,22 (2):195-201.
[69] Kopp J, Schwede T. The SWISS-MODEL Repository: new features and functionalities. Nucleic Acids Res, 2006,34(Database issue):D315-318.
[70] Yu F, Xu XF, Jin Z. Studies on the mechanism of thermostability and thermophilicity change of thermostable alkaline phosphatase and its mutants. Sheng Wu Gong Cheng Xue Bao, 2003 ,19(4):493-496.
[71]Sigrist CJ, Cerutti L, Hulo N, et al.PROSITE: a documented database using patterns and profiles as motif descriptors.Brief Bioinform, 2002, 3(3):265-274.
[72] Hulo N, Bairoch A, Bulliard V ,et al. The PROSITE database.Nucleic Acids Res, 2006, 34(Data base issue):D227-230.
[73]Quevillon E, Silventoinen V, Pillai S, et al.InterProScan: protein domains identifier.Nucleic Acids Res, 2005,33(Web Server issue):W116-120.
[74]Zdobnov EM, Apweiler R.InterProScan~an integration platform for the signature-recognition methods in InterPro.Bioinformatics, 2001,17(9):847-848.
[2]Ikekawa A,Ikekawa S.Fruits of human genome project and private venture,and their impact on life science.Yakugaku Zasshi,2001,121(12):845-873.
[3]Freeman K.Harnessing the HGP of public health.Environ Health Perspect,2004,112(7):A402.
[4]Luscombe NM,Greenbaum D,Gerstein M.What is bioinformatics? A proposed definition and overview of the field.Methods Inf Med,2001,40(4):346-358.
[5]Burkle T,Hain T,Hossain H,et al.Bioinformatics in medical practice:what is necessary for a hospital? Medinfo,2001,10(Pt2):951-955.
[6]Ashida H.What is bioinformatics?Rinsho Byori,2002,50(1):40-44.
[7]Qiang Lu,Pei Hao,Vasa Curcin,et al.KDE Bioscience:Platform for bioinformatics analysis workflows.Journal of Biomedical informatics,2006,39(4):440-450.
[8]王发生,毛君莲.生命科学时代的生物信息学.中国现代医学杂志,2000,10(12):108-109.
[9]Liebman MN.Biomedical informatics:the future for drug development.Drug Discov Today,2002,7(20 Suppl):S197-203.
[10]Wishart.Bioinformatics in drug development and assessment.Drug Metab Rev,2005,37(2):279-310.
[11]Volker C,Brown JR.Bioinformatics and the discovery of novel antimic-robial targets.Curr DrugTargets Infect Disord,2002,2(4):279-290.
[12]McCarthy FM,Wang N,Magee GB,et al.AgBase:a functional genomics resource for agriculture.BMC Genomics,2006,7:229
[13]Rhee SY,Dickerson J,Xu D.Bioinformatics and its applications in plant biology.Annu Rev Plant Bioi,2006,57:335-360.
[14]Li D,Lu GX,Fu JJ,et al.Molecular cloning and expression analysis of a novel human testis-Spcificgene.Yi Chuan Xue Bao,2004,31(6)545-551.
[15]Nie DS,Zhu WB,Xiang Y.Molecular cloning and primary functional analy-sis of a novel human testis-specific gene.Yi Chuan Xue Bao,2005,32(4):337-345.
[16]Li D,Lu GX.Identification and expression of a novel human testis-specific gene by digital differential display.Chin Med J(Engl),2004,117(12):1791-1796.
[17]Fu JJ,Lu GX,Li LY,et al.Molecular cloning for testis spermatogenesis cell apoptosis related gene TSARG1 and Mtsargl and expression analysis for Mtsargl gene.Yi Chuan Xue Bao,2003,30(1):25-29.
[18]Nie DS,Xiang Y,Wang J.Identification of a novel testis-specific gene mtLR1,which is expressed at specific stages of mouse spermatogenesis.Biochem Biophys Res Commun,2005,328(4):1010-1018.
[19]Benagiano G,Bastianelli C,Farris M.Infertility:a global perspective.Minerva Ginecol,2006,58(6):445-457
[20]Illions EH.Infertility:etiologies,evaluation and treatments.Drugs Today (Bare),2000,36(6):369-382.
[21]Krausz C,Degl'Innocenti S.Y chromosome and male infertility:update,2006.Front Biosci,2006,11:3049-3061.
[22]Aitken RJ,Skakkebaek NE,Roman SD.Male reproductive health and the environment.Med J Aust,2006,185(8):414-415.
[23]Sallmen M,Sandier DP,Hoppin JA,et al.Reduced fertility among overweight and obese men.Epidemiology,2006,17(5):520-523.
[24]Said TM,Ranga G,Agarwal A.Relationship between semen quality and tobacco chewing in men undergoing infertility evaluation.Fertil Steril,2005,84(3):649-653.
[25]Lenzi A,Lombardo F,Salacone P.et.al.Stress,sexual dysfunctions,and male infertility.J Endoerinol Invest,2003,26(3 Suppl):72-76.
[26]Trokoudes KM,Skordis N,Picolos MK.Infertility and thyroid disorders.Curr Opin Obstet Gynecol,2006,18(4):446-451.
[27]Engel W,Adham IM.Nayemia K.et al.Genetic causes of male infertility.Verb Dtsch Ges Pathol,2004,88:130-135.
[28]Ferlin A,Arredi B,Foresta C.Genetic causes of male infertility.Reprod Toxicol,2006,22(2):133-141.
[29]Lilford R,Jones AM,Bishop DT,et al.Case-control study of whether subfertility in men is familial.BMJ,1994,309(6954):570-573.
[30]Ekerhovd E.Infertility treatment of men with azoospermia.Tidsskr Nor Laegeforen,2006,126(12):1598-1601.
[31]Tiepolo L,Zuffardi O.Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm.Hum Genet,1976,34(2):119-124.
[32]Reijo R,Lee TY,Salo P,et al.Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene.Nat Genet,1995,10(4):383-393.
[33]邵敏杰,张颖.特发性无精子症少精子症患者分子遗传学及血清学的研究进展.中国优生与遗传杂志,2005,13(7):12-14.
[34]Kent-First M,Muallem A,Shultz J,et al.Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region(AZFd)by Y-chromosome microdeletion detection.Mol Reprod Dev,1999,53(1):27-41.
[35]崔英霞,王咏梅,徐建平,等.与精子发生障碍相关的染色体畸变.中华男科学,2001,7(2):99-101.
[36]Huminiecki L,Bicknell R.In silico cloning of novel endothelial-specific genes.GenomeRes,2000,10(11):1796-1806.
[37]Huang J,Wang JF,Zhang HS,et al.In silico cloning of glucose -6- phosphate dehydrogenase eDNA from rice(Oryza sativa L).Yi Chuan Xue Bao,2002,29(11):1012-1016.
[38]张成岗,贺福初.生物信息学方法与实践.北京:科学出版社,2002.16-17.
[39]Sun CX,Yu AC.A brief introduction to the methods for novel gene cloning.Sheng Li Ke Xue Jin Zhan,2000,31(1):35-42.
[40]Huang W,Fang XD,Zhao WM,et al.The methods of identifying differences in mRNA expression.Sheng Wu Gong Cheng Xue Bao,2002,18(4):521-524.
[41]Liang P,Pardee AB.Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction.Science,1992,257(5072):67-971.
[42]Velculescu VE,Zhang L,Vogelstein B,et al.Serial analysis of gene expression.Science,1995,270(5235):484-487.
[43]潘泽民,潘晓琳,杨磊,等.基因表达系列分析(SAGE)技术在肿瘤研究中的应用.生命的化学,2004,24(4):322-324.
[44]Diatchenko L,Lau YF,Campbell AP,et al.Suppression subtractive hybridization:a method for generating differentially regulated or tissue-specific cDNA probes and libraries.Proc Natl Acad Sci U S A,1996,93(12):6025-6030.
[45]杨春梅,万柏坤,梁慧嫒,等.DNA微阵列技术及其在生物医学中的应用.国外医学生物医学工程分册,2002,25(5)203-206.
[46]Liu SF,Li LY,Fu JJ,et al.Rapid identification of human testis spermatocyte apoptosis-related gene,TSARG2,by nested PCR and draft human genome searching,Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao, 2002,34(3):378-382.
[47]Liu G,Lu G,Fu J,et al.Molecular cloning of TSARG3 gene related to apoptosis in human spermatogenic cells,Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2003,20(2):107-110.
[48]Xing XW,Li LY,Fu JJ,et al.Cloning of eDNA of TSARG4,a human spermatogenesis related gene,Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao,2003,35(3):283-288.
[49]Zneimer SM.The human genome project:exploring its progress and successes and the ethical,legal,and social implications.Clin Leadersh Manag Rev,2002,16(3):151-157.
[50]Trent RJ.Milestones in the Human Genome Project:genesis to postgenome,Med J Aust,2000,173(11-12):591-594.
[51]Kulikova T,Aldebert P,Althorpe N.The EMBL Nueleotide Sequence Database.Nucleic Acids Res,2004,32(Database issue):D27-30.
[52]Johnson RS,Davis MT,Taylor JA.Informatics for protein identification by mass spectrometry.Methods,2005,35(3):223-236.
[53]Agarwal P,States DJ.Comparative accuracy of methods for protein sequence similarity search.Bioinformatics,1998,14(1):40-47.
[54]Webber C,Barton GJ.Increased coverage obtained by combination of methods for protein sequence database searching.Bioinformatics,2003,19(11):1397-1403.
[55]Contreras CF,Canales MA,Alvarez A.Molecular modeling of the amyloid-beta-peptide using the homology to a fragment of triosephosphate iso- merase that forms amyloid in vitro.Protein Eng,1999,12(11):959-966.
[56]江荣才,于士柱,浦佩玉,等.应用微阵列技术初步探讨间变性星形细胞瘤基因表达谱.中华病理学杂志,2004,33(4):371-372.
[57]江荣才,浦佩玉,焦保华,等.CDC10在胶质瘤中的表达.中国临床神经科学,2002,10(3):227-229.
[58]Rotmistrovsky K,Jang W,Schuler GD.A web server for performing electronic PCR.Nucleic Acids Res,2004,32(Web Server issue):W108-12.
[59]Martin J,Han C,Gordon LA,et al.The sequence and analysis of duplication-rich human chromosome 16.Nature,2004,432(7020):988-994.
[60]Takeuchi A,Mishina Y,Miyaishi O,et al.Heterozygosity with respect to Zfp148causes complete loss of fetal germ cells during mouse embryogenesis.Nat Genet,2003,33(2):172-176.
[61]Rovio AT,Marchington DR,Donat S,et al.Mutations at the mitochon- drial DNA polymerase(POLG)locus associated with male infertility.Nat Genet,2001,29(3):261-262.
[62]Sigrist CJ,Cerutti L,Hulo N,et al.PROSITE:a documented database using patterns and profiles as motif descriptors.Brief Bioinform,2002,3(3):265-274.
[63]Hulo N,Bairoch A,Bulliard V,et al.The PROSITE database.Nucleic Acids Res,2006,34(Data base issue):D227-230.
[64]Hu H,Yu WB,Li SX,et al.Crystallization and preliminary crystal-lographic studies of human septin 1 with site-directed mutations.Acta Crystallograph Sect F Struct Biol Cryst Commun,2006,62(Pt2):128-132.
[65]Huang YW,Surka MC,Reynaud D,et al.GTP binding and hydrolysis kinetics of human septin 2.FEBS J,2006,273(14):3248-3260.
[66]Douglas LM,Alvarez FJ,McCreary C,et al.Septin function in yeast model systems and pathogenic fungi.Eukaryot Cell,2005,4(9):1503-1512.
[67]Low C,Macara IG.Structural analysis of septin 2,6,and 7 comp- lexesJ Biol Chem,2006,281(41):30697-30706.
[68]Hall PA,Jung K,Hillan KJ,et al.Expression profiling the human septin gene family.J Pathol,2005,206(3):269-278.
[69]Martinez C,Ware J.Mammalian septin function in hemostasis and beyond.Exp Biol Med(Maywood),2004,229(11):1111-1119.
[70]Ono R,Ihara M,Nakajima H,et al.Disruption of Sept6,a fusion partner gene of MLL,does not affect ontogeny,leukemogenesis induced by MLL-SEPT6,or phenotype induced by the loss of Sept4.Mol Cell Biol,2005,25(24):10965-10978.
[71]Hall PA,Russell SE.The pathobiology of the septin gene family.J Pathol,2004,204(4):489-505.
[72]Kinoshita M.Assembly of mammalian septins.J Biochem(Tokyo),2003,134(4):491-496.
[73]Kremer BE,Haystead T,Macara IG.Mammalian septins regulate microtubule stability through interaction with the microtubule- binding protein MAP4.Mol Biol Cell,2005,16(10):4648-4659.
[74]Gladfelter AS,Zyla TR,Lew DJ.Genetic interactions among regulators of septin organization.Eukaryot Cell,2004,3(4):847-854.
[75]Craven RA,Hanrahan S,Totty N,et al.Proteomic identification of a role for the von Hippel Lindau tumour suppressor in changes in the expression of mitochondrial proteins and septin 2 in renal cell carcinoma.Proteomics,2006,6(13):3880-3893.
[76]Kim DS,Hubbard SL,Peraud A,et al Analysis of mammalian septin expression in human malignant brain tumors.Neoplasia,2004,6(2):168-78.
[77]Scott M,McCluggage WG,Hillan KJ,et al.Altered patterns of transcription of the septin gene,SEPT9,in ovarian tumorigenesis.Int J Cancer,2006,118(5):1325-1329.
[78]Kalikin LM,Sims HL,Petty EM.Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene(MSF)that map to a 17q25 region of loss in breast and ovarian tumors.Genomics,2000,63(2):165-172.
[79]Cerveim N,Correia C,Bizarro S,et al.SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23).Oncogene,2006,25(45):6147-6152.
[80]Gonzalez-Novo A,Jimenez J,Garcia MJ,et al.Dynamics of CaCdc10,a septin of Candida albieans,in living cells and during infecfion.Int Microbiol,2004,7(2):105-112.
[81]Takehashi M,Tanaka S,Stedeford T,et al.Expression of septin 3 isoforms in human brain.Gene Expr,2004,1(5-6):271-278.
[82]Kuhlenbaumer G,Hannibal MC,Nelis E,et al.Mutations in SEPT9 cause hereditary neuralgic amyotrophy.Nat Genet,2005,37(10):1044-1046.
[83]Kissel H,Georgescu MM,Larisch S,,et al.The Sept4 septin locus is required for sperm terminal differentiation in mice.Dev Cell,2005,8(3):353-364.
[84]Ihara M,Kinoshita A,Yamada S,et al.Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa.Dev Cell,2005,8(3):343-352.
[85]Lin YM,Teng YN,Lee PC,et al.AZFa candidate gene deletions in Taiwanese patients with spermatogenic failure.J Formos Med Assoc,2001,100(9):592-597.
[86]Krausz C,McElreavey K.Y chromosome and male infertility.Front Biosci,1999,4:E1-8.
[87]Fujisawa M,Shirakawa T,Kanzaki M,et al.Y-chromosome mierodeletion and phenotype in cytogenetically normal men with idiopathic azoospermia.Fertil Steril,2001,76(3):491-495.
[88]Taskiran C,Baltaci V,Gunalp S.Globozoospermia:Do Y-chromosome microdeletions play a role in this rare spermatogenic disorder?J Reprod Med,2006,1(8):628-634.
[89]Shafik A,Shafik AA,Shafik I,et al.ular andrology as related to sperm DNA fragmentation/sperm chromatin biotechnology.Arch Androl,2006,52(4):299-310.
[90]Melo KF,Mendonca BB,Billerbeck AE,et al.Androgen insensitivity syndrome:clinical,hormonal and molecular analysis of 33 cases.Arq Bras Endocrinol Metabol,2005,49(1):87-97.
[91]Seligman J,Page DC.The Dazh gene is expressed in male and female embryonic gonads before germ cell sex differentiation.Biochem Bio- phys Res Commun,1998,245(3):878-882.
[92]Yen PH,Chai NN,Salido EC.The human autosomal gene DAZLA:testis specificity and a candidate for male infertility.Hum Mol Genet,1996,5(12):2013-2017.
[93]Krausz C,Sassone-Corsi P.Genetic control of spermiogenesis:insi- ghts from the CREM gene and implications for human infertility.Reprod Biomed Online,2005,10(1):64-71.
[94]Blocher S,Fink L,Bohle RM,et al CREM activator and repressor isoform expression in human male germ cells.Int J Androl,2005,28(4):215-223.
[95]Dix DJ,Allen JW,Collins BW,et al.Targeted gene disruption of Hsp70-2 results in failed meiosis,germ cell apoptosis,and male infertility.Proc Natl Acad Sci U S A,1996,93(8):3264-3268.
[96]Zhu D,Dix DJ,Eddy EM.HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes.Development,1997,124(15):3007-3014.
[97]Aarabi M,Modarressi MH,Soltanghoraee H,et al.Testicular expre- ssion of synaptonemal complex protein 3(SYCP3)messenger ribonu- cleic acid in 110patients with nonobstructive azoospermia.Fertil Steril,2006,86(2):325-331.
[98]Miyamoto T,Hasuike S,Yogev L,et al.Azoospermia in patients heterozygous for a mutation in SYCP3.Lancet,2003,362(9397):1714-1719.
[99]Grimaldi P,Rossi P,Dolci S,et al.Molecular genetics of male infertility:stem cell factor/c-kit system.Am J Reprod Immunol,2002,48(1):27-33.
[100]宋宁宏,苏建堂.基因缺陷对精子发生的影响.国外医学,2003,23(2):176-179.
[1] Qiang Lu, Pei Hao, Vasa Curcin,et al.KDE Bioscience: Platform for bioin-formatics analysis workflows. Journal of Biomedical informatics , 2006, 39(4): 440-450.
[2] Liebman MN. Biomedical informatics: the future for drug development. Drug Discov Today, 2002 ,7(20 Suppl):S197-203.
[3] Wishart.Bioinformatics in drug development and assessment.Drug Metab Rev, 2005,37(2):279-310.
[4] Volker C,Brown JR.Bioinformatics and the discovery of novel anti-microbial targets. Curr Drug Targets Infect Disord,2002 ,2(4):279-290.
[5] McCarthy FM, Wang N, Magee GB, et al.AgBase: a functional genomics resource for agriculture. BMC Genomics,2006,7:229.
[6] Rhee SY,Dickerson J,Xu D. Bioinformatics and Its Applications in Plant Biology. Annu Rev Plant Biol,2005 ,[Epub ahead of print].
[7] Rajpal DK. Understanding biology through bioinformatics.Int J Toxicol, 2005, 24(3):147-152.
[8] Janet M.Thornton.Trends Guide To Bioinformatics,30-31.
[9] Benson DA,Karsch-Mizrachi,Lipman DJ, et al. GenBank. Nucleic Acids Res 2006,34(Database issue):D16-20.
[10]Letovsky SI,Cottingham RW,Porter CJ,et.al. GDB: the Human Genome Database. Nucleic Acids Res, 1998 ,26(1):94-9.
[11]Cuticchia AJ. Future vision of the GDB human genome database. Hum Mutat, 2000,15(1):62-67.
[12]Rabhan M,Chalifa-Caspi V,Prilusky J, et al. GeneCards: integrating information about genes, proteins and diseases.Trends Genet, 1997,13(4):163.
[13] White O,Kerlavage AR. TDB: new databases for biological discovery. Methods Enzymol, 1996,266:27-40.
[14] Wheeler DL,Barrett T,Benson DA,et al. Database resources of the National Center for Biotech- nology Information.Nucleic Acids Res, 2006,34(Database issue):D173-180.
[15]Apweiler R,Bairoch A,Wu CH.Protein sequence databases. Curr Opin Chem Biol,2004,8(1):76-80.
[16]Boeckmann B,Bairoch A,Apweiler R,et al.The SWISS-PROT protein knowle- dgebase and its supplement TrEMBL in 2003.Nucleic Acids Res,2003,31(1):365-370.
[17]Boeckmann B,Bairoch A,Apweiler R,et al.The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003,Nucleic Acids Res,31(1):365-370.
[18]Schneider M,Tognolli M,Bairoch A,et al.The Swiss-Prot protein knowledgebase and ExPASy:providing the plant community with high quality proteomic data and tools.Plant Physiol Biochem,2004,42(12):1013-1021.
[19]Apweiler R,Bairch A,Wu CH,et al.UniProt:the Universal Protein knowle-dgebase.Nucleic Acids Res,2004,32(Database issue):D115-119.
[20]Bairch A,Apweiler R,Wu CH,et al.The Universal Protein Resource(UniProt).Nucleic Acids Res,2005,33:D154-159.
[21]O'Donovan C,Martin MJ,Gattiker,et al.High-quality protein knowledge resource:SWISS-PROT and TrEMBL.Bdef Bioinform,2002,3(3):275-284.
[22]Berman HM,Battistuz T,Bhat TN,et al.The Protein Data Bank.,Acta Crystallogr D Biol Crystallogr,2002,58(Pt 6 No 1):899-907.
[23]Andreeva A,Howorth D,Brermer SE,et al.SCOP database in 2004:refinements integrate structure and sequence family data.Nucleic Acids Res,2004,32(Database issue):D226-229.
[24]Ison JC.Exploring protein domain structure..Bdef Bioinform,2000,1(3):305-312.
[25]Stoesser G,Baker W,Vab den Broek A,et al.The EMBL nucleotide sequence database.Nucleic Acids Res,2001,29(1):17-21.
[26]Geer RC,Sayers EW.Entrez:making use of its power.Brief Bioinform,2003,4(2):179-184.
[27]张成岗,贺福初.生物信息学方法与实践.北京:科学出版社,2002:16-17.
[28]To KY.Identification of differential gene expression by high throughput analysis.Comb Chem High Throughput Screen,2000,3(3):235-241.
[29]Li D,Lu GX,Fu JJ,et al.Molecular cloning and expression analysis of a novel human testis-Spcific gene.Yi Chuan Xue Bao,2004,31(6):545-551.
[30]Nie DS,Zhu WB,Xiang Y.Molecular cloning and primary functional analysis of a novel human testis-specific gene.Yi Chuan Xue Bao,2005,32(4):337-345.
[31]LiD,Lu GX.Identification and expression of a novel human testis-specific gene by digital diferenfial display.Chi n Med J(Engl),2004,117(12):1791-1796.
[32]Fu JJ,Lu GX,Li LY,et al.Molecular cloning for testis spermatogenesis cell apoptosis related gene TSARG1 and Mtsargl and expression analysis for Mtsargl gene. Yi Chuan Xue Bao,2003,30(1):25-29.
[33]Nie DS,Xiang Y,Wang J. Identification of a novel testis-specific gene mtLR1, which is expressed at specific stages of mouse spermatogenesis.Biochem Biophys Res Commun, 2005 ,328(4):1010-1018.
[34]Scheurle D,DeYoung MP,Binninger DM, , et al. Cancer gene discovery using digital differential display.Cancer Res, 2000 ,60(15):4037-4043.
[35]Schaefer C,Grouse L,Buetow K,et al.A new cancer genome anatomy project web resourse for the Community,Cancer J,2001,7(1):52-60.
[36]Strausberg RL.The Cancer Genome Anatomy Project:new resources for reading the molecular signatures of cancer.J Pathol,2001,195(1):31-40.
[37]Schaefer C,Grouse L,Buetow K. A new cancer genome anatomy project web resource for the community.Cancer J, 2001,7(1):52-60.
[38]Riggins GJ. Using Serial Analysis of Gene Expression to identify tumor markers and antigens. Dis Markers, 2001,17(2) :41-48.
[39]De Young MP,Damania H,Scheurle D.bioinformatics-Based discovery of a novel factor with apparent specificity to colon cancer,2002,16(4):239-248.
[40] Stekel DJ,Git Y, Falciani F, The comparison of gene expression from multiple cDNA libraries.Genome Res, 2000,10(12):2055-2061.
[41]Kulikova T,Aldebert P,Althorpe N. The EMBL Nucleotide Sequence Database.Nucleic Acids Res, 2004,32(Database issue):D27-30.
[42] Johnson RS, Davis MT, Taylor JA. Informatics for protein identification by mass spectrometry. Methods, 2005,35(3):223-236.
[43]Agarwal P,States DJ. Comparative accuracy of methods for protein sequence similarity search. Bioinformatics, 1998;14(1):40-47.
[44] Chen TG,Wu SF,Wan P.Gene prediction and function research of SARS-CoV(BJ01). Yi Chuan Xue Bao,2003,30(8):773-780.
[45]Agarwal P,States DJ. Comparative accuracy of methods for protein sequence similarity search. Bioinformatics, 1998,14(1):40-47.
[46]Contreras CF, Canales MA, Alvarez A.Molecular modeling of the amyloid-beta-peptide using the homology to a fragment of triosephosphate isomerase that forms amyloid in vitro. Protein Eng, 1999 ,12(11):959-966.
[47] Burke J,Davison,Hide W. d2_cluster: a validated method for clustering EST and full-length cDNAsequences.Genome Res, 1999,9(11):1135-1142.
[48]Rotmistrovsky K,Jang W,Schuler GD.A web server for performing electronic PCR.Nucleic Acids Res,2004,32(Web Server issue):W108-12.
[49]Wheeler DL,Church DM,Federhen S.Database resources of the National Center for Biotechnology.Nucleic Acids Res,2003,31(1):28-33.
[50]Guigo R,Agarwal P,Abril JF.An assessment of gene prediction accuracy in large DNA sequences.Genome Res,2000,10(10):1631-1642.
[51]Burge C,Karlin S.Prediction of complete gene structures in human genomic DNA.J Mol Biol,1997,268(1):78-94.
[52]Schmid CD,Perier R,Praz V,et al.EPD in its twentieth year:towards complete promoter coverage of selected model organisms.Nucleic Acids Res,2006,34(Database issue):D82-85.
[53]Wingender E.TRANSFAC,TRANSPATH and CYTOMER as starting points for an ontology of regulatory networks.In Silico Biol,2004;4(1):55-61.
[54]Fogel GB,Weekes DG,Varga G,et al.A statistical analysis of the TRANSFAC database.Biosystems,2005,81(2):137-154.
[55]Pesole G,Liuni S,D'Souza M.PatSearch:a pattern matcher software that finds functional elements in nucleotide and protein sequences and assesses their statistical significance.Bioinformatics,2000,16(5):439-450.
[56]Grillo G,Licciulli F,Liuni S,PatSearch:A program for the detection of patterns and structural motifs in nucleotide sequences.Nucleic Acids Res,2003,31(13):3608-3612.
[57]Wishart DS,Fortin S.The BioTools Suite.A comprehensive suite of latform-independent bioinformatics tools.Mol Biotechnol,2001,19(1):59-77.
[58]Wishart DS,Stothard P,Van Domselaar GH.PepTool and GeneTool:platform-independent tools for biological sequence analysis.Methods Mol Biol,2000,132:93-113.
[59]Lu G,Moriyama EN.Vector NTI,a balanced all-in-one sequence analysis suite.Brief Bioinform,2004,5(4):378-388.
[60]Ikeda M,Arai M,Lao DM,et al.Transmembrane topology prediction methods:a re-assessment and improvement by a consensus method using a dataset of experimentally-characterized transmembra- ne topologies.In Silico Biol,2002,2(1):19-33.
[61]Bertaccini E,Trudell JR.Predicting the transmembrane secondary structure of ligand-gated ion channels.Protein Eng,2002,15(6):443-454.
[62]Tusnady GE, Simon I. The HMMTOP transmembrane topology prediction server.Bioinformatics, 2001,17(9):849-850.
[63]Rost B, Yachdav G, Liu J. The PredictProtein server.Nucleic Acids Res, 2004,32(Web Server issue):W321-326.
[64]Emanuelsson O, Nielsen H, Brunak S. Predicting subcellular localization of proteins based on their N-terminal amino acid sequence.J Mol Biol, 2000 , 300(4):1005-1016.
[65]Berjanskii MV, Neal S, Wishart DS. PREDITOR: a web server for predicting protein torsion angle restraints.Nucleic Acids Res, 2006 ,34(Web Server issue): W63-69.
[66] Zhang CT, Zhang R. A graphic approach to evaluate algorithms of secondary structure prediction. J Biomol Struct Dyn, 2000,17(5):829-842.
[67]Rost B, Liu J. The PredictProtein server.Nucleic Acids Res, 2003,31 (13):3300-3304.
[68] Arnold K, Bordoli L, Kopp J, et al.The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling.Bioinformatics, 2006 ,22 (2):195-201.
[69] Kopp J, Schwede T. The SWISS-MODEL Repository: new features and functionalities. Nucleic Acids Res, 2006,34(Database issue):D315-318.
[70] Yu F, Xu XF, Jin Z. Studies on the mechanism of thermostability and thermophilicity change of thermostable alkaline phosphatase and its mutants. Sheng Wu Gong Cheng Xue Bao, 2003 ,19(4):493-496.
[71]Sigrist CJ, Cerutti L, Hulo N, et al.PROSITE: a documented database using patterns and profiles as motif descriptors.Brief Bioinform, 2002, 3(3):265-274.
[72] Hulo N, Bairoch A, Bulliard V ,et al. The PROSITE database.Nucleic Acids Res, 2006, 34(Data base issue):D227-230.
[73]Quevillon E, Silventoinen V, Pillai S, et al.InterProScan: protein domains identifier.Nucleic Acids Res, 2005,33(Web Server issue):W116-120.
[74]Zdobnov EM, Apweiler R.InterProScan~an integration platform for the signature-recognition methods in InterPro.Bioinformatics, 2001,17(9):847-848.
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