人類腫瘤的鼠模型網(wǎng)絡(luò)入口鼠的腫瘤生物學(xué)數(shù)據(jù)庫

1、.：.；人類腫瘤的鼠模型網(wǎng)絡(luò)入口:鼠的腫瘤生物學(xué)數(shù)據(jù)庫生命科學(xué)學(xué)院2002級生物技術(shù) 曹文瑞 學(xué)號:021402153摘要鼠的腫瘤生物學(xué)數(shù)據(jù)庫MTB提供有遺傳詳細(xì)闡明(即先天性,轉(zhuǎn)基因和有目的的突變種)的老鼠種群腫瘤遺傳學(xué)和病理學(xué)的詳細(xì)信息資源。這個數(shù)據(jù)庫中的數(shù)據(jù)資源包括曾經(jīng)發(fā)表的科學(xué)文獻(xiàn)以及科學(xué)團(tuán)體的直接的數(shù)據(jù)論據(jù)。研討者利用基于環(huán)球網(wǎng)的訊問窗體訪問MTB，他們可以利用這個數(shù)據(jù)庫回答諸如“對基于C57BL/6J背景發(fā)明的轉(zhuǎn)基因老鼠的腫瘤有哪些報道？，“老鼠中哪些腫瘤與Trp53 基因的突變有關(guān)？和“在不思索遺傳背景的情況下，有哪些乳腺腫瘤的病理模型是可用的？之類的問題。鼠的腫瘤生物學(xué)數(shù)據(jù)庫自

2、1998年在鼠基因組信息學(xué)網(wǎng)站( HYPERLINK )上提供運(yùn)用。最近我們對MTB進(jìn)展了一些改良，包括新的查詢選項(xiàng)、重新設(shè)計的查詢窗體和病理學(xué)及遺傳學(xué)數(shù)據(jù)的結(jié)果界面、添加了病理學(xué)數(shù)據(jù)的電子數(shù)據(jù)論據(jù)和注解工具。導(dǎo)言實(shí)驗(yàn)室中老鼠曾經(jīng)被用作研討人類疾病的模型有很長時間了，這是由于他們在生理上、在基因組的容量和組織上與人類類似，并且易于在遺傳上進(jìn)展改造、易于實(shí)驗(yàn)操作?？梢源_切的反映人類癌癥和組織病理學(xué)的發(fā)育中的鼠模型是1998年由國家癌癥學(xué)會一次“偶爾的時機(jī)發(fā)現(xiàn)的。鼠模型提供了探求疾病進(jìn)展過程中遺傳及細(xì)胞方面的變化以及對有能夠運(yùn)用于臨床的治療戰(zhàn)略進(jìn)展測試的手段。不同的鼠純系株在腫瘤易感性方面有很大不

3、同。規(guī)范的鼠純系通常并不是人類腫瘤的恰當(dāng)模型，這是由于鼠中零星腫瘤的低頻率和較晚的發(fā)作時間。雖然如此，對特殊遺傳背景下腫瘤特征方式的了解對于選擇用于得到疾病進(jìn)展方式更有利于建造人類特殊疾病的遺傳及分子模型的轉(zhuǎn)基因或靶突變的適宜鼠種系是重要的。許多關(guān)于有遺傳詳細(xì)闡明(即先天性,轉(zhuǎn)基因和有目的的突變種)的鼠腫瘤易感性和抗性的數(shù)據(jù)在允許研討者對不同鼠品系進(jìn)展比較或比較規(guī)范鼠純品系和基于同樣先天背景建造的轉(zhuǎn)基因或定點(diǎn)突變鼠品系癌癥方式的方式下是不可用的。將連成一體的關(guān)于有遺傳詳細(xì)闡明的鼠品系遺傳和病理生物學(xué)的不同數(shù)據(jù)放入一個可查詢的數(shù)據(jù)庫是MTB第一位的義務(wù)。在最近的一項(xiàng)對腫瘤遺傳學(xué)研討的網(wǎng)絡(luò)資源的調(diào)

4、查中，我們發(fā)現(xiàn)了70余個與根底腫瘤遺傳學(xué)研討相關(guān)的數(shù)據(jù)庫和信息資源。大多數(shù)現(xiàn)有腫瘤相關(guān)資源和數(shù)據(jù)庫集中于單個基因或特殊的腫瘤性狀。在我們調(diào)查的站點(diǎn)中，僅有少數(shù)提供關(guān)于人腫瘤鼠模型的信息；提供實(shí)驗(yàn)室老鼠病理生物學(xué)詳細(xì)信息的站點(diǎn)那么更少。在提供有關(guān)腫瘤遺傳學(xué)和病理學(xué)的綜合數(shù)據(jù)的范圍和深度上，MTB在現(xiàn)有的資源中是獨(dú)一無二的。MTB自1998年以來就可以經(jīng)過環(huán)球網(wǎng)方便的運(yùn)用。出現(xiàn)于MTB中的最初數(shù)據(jù)是腫瘤類別、老鼠品系、遺傳學(xué)、病理學(xué)和參考文獻(xiàn)已發(fā)表和未發(fā)表的文獻(xiàn)都包含于這個數(shù)據(jù)庫中。這些方面代表了查詢此數(shù)據(jù)庫的基于網(wǎng)絡(luò)的窗體的主要內(nèi)容。MTB是用于描畫由Jackson實(shí)驗(yàn)室鼠基因組信息MGI組織建

5、立的實(shí)驗(yàn)室老鼠品系遺傳及生物學(xué)信息的信息學(xué)下部構(gòu)造的延伸。MTB中鼠基因和品系的命名法于鼠基因數(shù)據(jù)庫( HYPERLINK /mgihome/nomen /mgihome/nomen)描畫的鼠的正式命名法。數(shù)據(jù)庫中運(yùn)用的解剖學(xué)術(shù)語于基因表達(dá)數(shù)據(jù)庫GXD鼠解剖學(xué)控制性詞匯。MTB中的許多病理學(xué)和診斷學(xué)術(shù)語于一本權(quán)威的教科書衰老鼠的病理學(xué)。2000年對MTB的改良關(guān)于MTB的設(shè)計和實(shí)施細(xì)節(jié)已在別處引見。這篇報告的目的是引見MTB的新特征和對它的改良。我們在過去一年我們收到的數(shù)據(jù)庫運(yùn)用者的最普遍的意見是提供額外的查詢選項(xiàng)和對病理學(xué)及遺傳學(xué)數(shù)據(jù)的報道。運(yùn)用者還要求我們重新設(shè)計一些數(shù)據(jù)摘要頁面以便使他們

6、不用經(jīng)過如此多的超文本鏈接得到他們想要的信息。根據(jù)用戶反響意見而作出的對系統(tǒng)的改動細(xì)節(jié)將在下面進(jìn)展闡明。對這些變化進(jìn)展闡明的網(wǎng)絡(luò)鏈接可以在本文的在線版本中看到增補(bǔ)資料。腫瘤類型查詢的新查詢選項(xiàng)我們實(shí)現(xiàn)了對腫瘤類型查詢選項(xiàng)兩個方面的改良。首先，我們添加了經(jīng)過解剖學(xué)體系而不僅僅是器官稱號查詢數(shù)據(jù)庫的才干。運(yùn)用者如今可以提交如“從MTB中找到一切消化系統(tǒng)腫瘤的信息之類的查詢。第二，我們添加了對基于腫瘤轉(zhuǎn)移形狀查詢限制的支持。例如，如今搜索知的分散到肺或肝臟的乳腺瘤成為能夠。對病理學(xué)查詢的改良在早先的MTB版本中，運(yùn)用者可以僅僅查詢和查看特殊的種/腫瘤結(jié)合的顯微照片和診斷記錄例如，“顯示一切FVBN-

7、TgN(MMTVPyVT)634Mul雌性轉(zhuǎn)基因鼠的乳腺癌種類。在2000年十月的數(shù)據(jù)庫版本中，我們添加了新的查詢窗體允許運(yùn)用者用更加普通規(guī)范包括器官稱號如“找到一切物種的肝臟腫瘤的病理學(xué)圖像、品系稱號如“找一切可用的BALB/c品系一切器官系統(tǒng)和一切類型的腫瘤和腫瘤類型如“找一切可用的一切物種的乳腺癌病理學(xué)數(shù)據(jù)搜索病理學(xué)數(shù)據(jù)。經(jīng)過這項(xiàng)改良，數(shù)據(jù)庫運(yùn)用者可以在MTB中經(jīng)過一項(xiàng)查詢產(chǎn)生關(guān)于病理學(xué)數(shù)據(jù)廣泛查詢的結(jié)果而不用需一次找一個腫瘤/品系組合。MTB中對病理學(xué)數(shù)據(jù)陳說的第二項(xiàng)改良與對組織學(xué)圖像的顯示相關(guān)聯(lián)。在早先的數(shù)據(jù)庫版本中，運(yùn)用者需求在病理學(xué)摘要頁面用鼠標(biāo)點(diǎn)擊一個組織學(xué)圖像極小的版本來查看

8、一個對細(xì)胞容顏有更高分辨率的圖像。具有更高分辨率圖像會替代當(dāng)前窗口，運(yùn)用者不能再對圖像和為圖像提供的診斷正文進(jìn)展比較。我們實(shí)現(xiàn)了對這種進(jìn)退兩難的局面的簡單處理方法，運(yùn)用者可以經(jīng)過用鼠標(biāo)點(diǎn)擊一個位于極小版本的顯微圖片下方的標(biāo)有“查看更大圖片的按鈕在一個獨(dú)立窗口中查看更高分辨率的圖像和診斷正文。這個顯示更高分辨率圖像的獨(dú)立窗口可以調(diào)整大小、可以獨(dú)立于網(wǎng)站主頁而封鎖。對基因查詢的改良在MTB數(shù)據(jù)庫的概念和邏輯設(shè)計中，我們過去把腫瘤細(xì)胞中遺傳改動的概念從與某一特定品系老鼠的背景相關(guān)的遺傳學(xué)中分別出來。結(jié)果，對MTB中品系查詢和以基因稱號或符號表示的腫瘤查詢都感興趣的用戶需求用兩種不同的查詢窗體進(jìn)展搜索

9、。我們實(shí)現(xiàn)了一種允許用戶用基因符號同時搜索品系和腫瘤信息。例如，用基因符號在MTB中搜索眼癌1Rb1基因可以得到帶有靶突變，誘發(fā)突變或是自然突變的Rb1基因的品系的信息和已報道的在Rb1基因中發(fā)生遺傳改動如點(diǎn)突變，缺失等的腫瘤的信息?；蚍柕牟樵兘Y(jié)果以兩部分被前往。首先，MTB中所記錄的基因的等位基因列表被前往。第二，這些等位基因與腫瘤和/或品系的聯(lián)絡(luò)會連同適當(dāng)詳細(xì)頁面的超文本鏈接一同顯示。對腫瘤發(fā)生頻率表格的改良MTB腫瘤發(fā)生頻率表格作為查詢和顯示鼠純系株家族復(fù)雜的癌癥方式信息的圖表手段于1999年提出的。腫瘤發(fā)生頻率表格包括大多數(shù)作為以建立通常運(yùn)用和遺傳上多樣的實(shí)驗(yàn)室鼠純系的根本表形數(shù)據(jù)

10、為目的的廣泛國際協(xié)作也稱為鼠“表型組的一部分被系統(tǒng)描畫的鼠純系株。我們對腫瘤發(fā)生頻率表格做了兩項(xiàng)改良以使它為我們的用戶提供更多的信息。首先，我們將表格從用三色編碼反映腫瘤發(fā)生頻率的系統(tǒng)變?yōu)槲迳幋a系統(tǒng)。五種顏色的顯示方式為用圖表交流腫瘤發(fā)生頻率提供了更加準(zhǔn)確的信息，還有一個額外的益處，就是即使圖表以黑白方式打印或顯示也容易區(qū)分它們的相對發(fā)生頻率。第二，我們對表格中的種系清單進(jìn)展了重新構(gòu)造，使它們由以字母順序排序變?yōu)橐约兿抵甑南底V關(guān)系分組。這種組織方式使尋覓預(yù)期在腫瘤易感性方式比較類似的種系。病理學(xué)信息的電子數(shù)據(jù)論據(jù)：JaxPathMTB最初獲得信息的方式是經(jīng)過腫瘤生物學(xué)和鼠遺傳學(xué)方面的專家級生

11、物學(xué)家對已發(fā)表科學(xué)文獻(xiàn)的進(jìn)展定期回想。為了給病理學(xué)信息提供電子論據(jù)和共有的查詢方法，我們發(fā)明了一個從MTB主頁容易進(jìn)入的基于網(wǎng)絡(luò)的數(shù)據(jù)庫JaxPath。JaxPath允許用戶向MTB提交未發(fā)表的病理學(xué)圖像和數(shù)據(jù)，或者或者添加由于空間或費(fèi)用緣由而沒有包含于初始發(fā)表文章之內(nèi)的增補(bǔ)圖像。向JaxPath提交數(shù)據(jù)的運(yùn)用者會被分配一個允許他們經(jīng)過網(wǎng)絡(luò)對投稿的闡明和注解進(jìn)展編輯的密碼。對投稿者圖片和注解的援用會在網(wǎng)站的病理學(xué)數(shù)據(jù)摘要中顯示。利用MTB進(jìn)展查詢ID的添加就像在以前的一篇MTB的報告中提到的那樣數(shù)據(jù)庫中每一腫瘤的實(shí)例都以腫瘤稱號、品系、性別和腫瘤來源器官的組合進(jìn)展描畫的。MTB中這種組織信息的

12、方式反映了我們的遺傳背景在腫瘤發(fā)生方式中發(fā)揚(yáng)重要作用的根本想象。MTB中每一腫瘤實(shí)例都被自動分派到一個允許我們明白無誤地指定該腫瘤并建立通往其它數(shù)據(jù)庫的穩(wěn)定鏈接的標(biāo)識符這些添加的標(biāo)識符在許多查詢結(jié)果頁面中顯示中。曾經(jīng)在他們感興趣經(jīng)過常規(guī)方法進(jìn)展查詢的數(shù)據(jù)庫中鑒別出特定記錄的運(yùn)用者如今可以可用適宜的MTB新增ID直接查詢MTB。未來研討方向國家腫瘤學(xué)會最近成立了人類腫瘤鼠模型協(xié)會MMHCC，并把它作為加速人腫瘤鼠模型建立和完成腫瘤稱號和診斷術(shù)語一致命名法的機(jī)構(gòu)。MMHCC正在建造一個將包括關(guān)于治療藥物檢測和在MTB范圍以外的實(shí)驗(yàn)草案信息的人腫瘤鼠模型數(shù)據(jù)庫，雖然它如今還不易為公眾運(yùn)用。由于許多將

13、在MMHCC中描畫的鼠品系也將在MTB中有所記錄，未來一年我們數(shù)據(jù)庫小組的一個組要義務(wù)就是將MTB銜接到MMHCC。這兩個數(shù)據(jù)庫的綜合將允許用戶無過失地從根本癌癥表型和遺傳信息轉(zhuǎn)向詳細(xì)記述的臨床前和臨床鼠模型、實(shí)驗(yàn)草案和治療實(shí)驗(yàn)結(jié)果。參考文獻(xiàn)1 Paigen,K. (1995) A miracle enough: the power of mice. Nature Med., 1, 215220. HYPERLINK /cgi/external_ref?access_num=A1995QX55900026&link_type=ISI ISI HYPERLINK /cgi/external_re

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19、T., Kadin,J.A., Richardson,J.E. and the Gene Expression Database Group. (2000) GXD: a gene expression database for the laboratory mouse: current status and recent enhancements. NucleicAcids Res., 28, 115119. Updated article in this issue: Nucleic Acids Res. (2001), 29, 98101. HYPERLINK /cgi/ijlink?l

20、inkType=ABST&journalCode=nar&resid=28/1/115 Abstract/Free FullText 9 Mohr,U., Dungworth,D.L., Capen,C.C., Carlton,W.W., Sundberg,J.P. and Ward,J.M. (1996) Pathobiology of the Aging Mouse. International Life Science Institute, Washington, DC, USA, vols 1 and 2. 10 Paigen,K. and Eppig,J.T. (2000) A mo

21、use phenome project. Mamm.Genome, 11, 715717. HYPERLINK /cgi/external_ref?access_num=000089003800001&link_type=ISI ISI HYPERLINK /cgi/external_ref?access_num=10967127&link_type=MED Medline 11 Beck,J.A., Lloyd,S., Hafezparast,M., Lennon-Pierce,M., Eppig,J.T., Festing,M.F.W. and Fisher,M.C. (2000) Gen

22、ealogies of mouse inbred strains. Nature Genet., 24, 2325. HYPERLINK /cgi/external_ref?access_num=000084609200010&link_type=ISI ISI HYPERLINK /cgi/external_ref?access_num=10615122&link_type=MED MedlineWeb-based access to mouse models of human cancers: the Mouse Tumor Biology (MTB) Database Carol J.

23、Bult HYPERLINK /cgi/content/full/29/1/95 l FN1#FN1 *, Debra M. Krupke, Dieter Nf, John P. Sundberg and Janan T. Eppig The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA Received October 3, 2000; Accepted October 4, 2000. ABSTRACTThe Mouse Tumor Biology (MTB) Database serves as a cura

24、ted, integrated resource for information about tumor genetics and pathology in genetically defined strains of mice (i.e., inbred, transgenic and targeted mutation strains). Sources of information for the database include the published scientific literature and direct data submissions by the scientif

25、ic community. Researchers access MTB using Web-based query forms and can use the database to answer such questions as What tumors have been reported in transgenic mice created on a C57BL/6J background?, What tumors in mice are associated with mutations in the Trp53 gene? and What pathology images ar

26、e available for tumors of the mammary gland regardless of genetic background?. MTB has been available on the Web since 1998 from the Mouse Genome Informatics web site ( HYPERLINK ). We have recently implemented a number of enhancements to MTB including new query options, redesigned query forms and r

27、esults pages for pathology and genetic data, and the addition of an electronic data submission and annotation tool for pathology data. INTRODUCTION The laboratory mouse has long served as an important animal model for human disease because it is known to resemble humans physiologically, is highly si

28、milar to humans in both genome content and organization, is well characterized genetically and is easily manipulated experimentally ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C1#GKE019C1 1). Developing mouse models that accurately reflect the genetics and histopathology of human cancers was recog

29、nized in 1998 as an exceptional opportunity by the National Cancer Institute ( HYPERLINK ) ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C2#GKE019C2 2). Mouse models provide the means to explore genetic and cellular aspects of disease progression and to test therapeutic strategies that might ultimat

30、ely be used clinically in humans ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C2#GKE019C2 2, HYPERLINK /cgi/content/full/29/1/95 l GKE019C3#GKE019C3 3). Different inbred strains of mice vary in their intrinsic tumor susceptibility. Standard inbred mice are not usually appropriate models for human c

31、ancers because of the relatively low frequency and late onset of sporadic cancers in mice. However, knowing the characteristic cancer profile of a particular genetic background is critical to the process of selecting the appropriate mouse strain for developing transgenic or targeted mutation mice wh

32、ose disease progression patterns may be more useful for modeling genetic and molecular aspects of a specific human disease. Much of the data about tumor susceptibility and resistance in genetically defined strains of mice (i.e., inbred lines, transgenics, targeted mutation strains) are not available

33、 in a format that allows researchers to compare different strains of mice to one another or to compare the cancer profile of a standard inbred strain to that of a transgenic or targeted mutation line created on the same inbred background. Integrating diverse data about genetics and pathobiology for

34、genetically defined strains of mice in a queryable database system is the primary mission of the Mouse Tumor Biology (MTB) Database ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C4#GKE019C4 4, HYPERLINK /cgi/content/full/29/1/95 l GKE019C5#GKE019C5 5). In a recent survey of Web-based resources for c

35、ancer genetics research, we identified over 70 databases and information resources related to basic cancer genetics research ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C6#GKE019C6 6). The majority of existing cancer-related resources and databases focus on single genes or specific cancer syndrome

36、s. Only a handful of the sites we surveyed provided information about mouse models of human cancers; even fewer sites provided detailed information about the pathobiology of laboratory mice. The MTB Database is unique among existing resources in both its scope and degree of integration of data about

37、 cancer genetics and pathology in laboratory mice. The MTB Database has been accessible via the World Wide Web since 1998 ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C5#GKE019C5 5). The primary data types represented in MTB are tumor types, mouse strain, genetics, pathology and references (both pu

38、blished and unpublished references are included in the database). These areas, in turn, represent the main Web-based forms that are used to query the database. MTB is an extension of the informatics infrastructure developed for representing genetic and biological information about the laboratory mou

39、se established by the Mouse Genome Informatics (MGI) Group at The Jackson Laboratory ( HYPERLINK ). The nomenclature used in MTB for genes and strains of mice comes from the official mouse nomenclature represented in the Mouse Genome Database ( HYPERLINK /mgihome/nomen /mgihome/nomen) ( HYPERLINK /c

40、gi/content/full/29/1/95 l GKE019C7#GKE019C7 7). Anatomical terms used in the database come from a controlled vocabulary of mouse anatomy supported by the Gene Expression Database (GXD) ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C8#GKE019C8 8). Much of the pathology and diagnostic terminology used

41、 in MTB comes from the Pathobiology of the Aging Mouse ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C9#GKE019C9 9), a standard mouse pathology text. ENHANCEMENTS TO MTB IN 2000Details concerning the design and implementation of MTB have been described elsewhere ( HYPERLINK /cgi/content/full/29/1/95

42、 l GKE019C4#GKE019C4 4, HYPERLINK /cgi/content/full/29/1/95 l GKE019C5#GKE019C5 5). The purpose of this report is to describe new features and recent enhancements to MTB. The most common input we received from our database users during the past year was to provide additional query options and report

43、s for pathology and genetic data. Users also requested that we redesign some of the data summary pages so that they did not have to follow as many hypertext links to retrieve the information they were seeking. The details of the changes to the system in response to user feedback are described below.

44、 Screen shots and web links illustrating these changes can be viewed in the online version of this article (Supplementary Material). New query options for tumor type searchesWe have implemented two enhancements to the query options for tumor types. First, we added the capacity to search the database

45、 by anatomical system instead of just by organ name. Users can now submit queries such as Retrieve all information from MTB for tumors of the Digestive System. Second, we added support for constraints on queries based on the status of metastases of a tumor. It is now possible, for example, to search

46、 for tumors of the mammary gland that are known to metastasize to the lung or the liver. Enhancements to pathology queriesIn the previous versions of MTB, users could only query for and view photomicrographs and diagnostic descriptions for specific strain/tumor combinations (e.g., Show me all mammar

47、y gland adenocarcinomas for FVBN-TgN(MMTVPyVT)634Mul female transgenic mice). In the October 2000 release of the database, we added new query forms to allow users to search for pathology data by more general criteria, including organ system (e.g., Retrieve all pathology images for tumors of the live

48、r regardless of strain), strain name (e.g., Retrieve all available pathology images for tumors in BALB/c mice regardless of organ system or type of tumor) and tumor type (e.g., Retrieve all available pathology data for mammary gland adenocarcinomas regardless of strain). With this enhancement, datab

49、ase users can now generate results for broad queries about the pathology data in MTB with a single query instead of having to retrieve tumor/strain combinations one at a time. A second enhancement to the representation of pathology data in MTB relates to the display of the histology images themselve

50、s. In previous versions of the database, users would mouse click on a thumbnail version of the histology images in a pathology summary page to view a version of the image with higher resolution of the cellular features. The higher resolution image replaced the current window and the user could no lo

51、nger compare the image with the diagnostic text provided for the image. We have implemented a simple solution to this dilemma in which the user can view the higher resolution image and diagnostic text in a separate window by mouse clicking on a button labeled View Large Image that is below the thumb

52、nail version of the photomicrograph. The separate window displaying the higher resolution image can be resized and closed independently of the main web page. Enhancements to gene queriesIn both the conceptual and logical design of the MTB database we separated the concepts of genetic changes in tumo

53、r cells from the genetics associated with the background of a particular strain of mouse. As a result, users interested in querying both strains and tumors represented in MTB by gene name or symbol needed to search the database using two different query forms. We have implemented a new query mechani

54、sm that allows users to search strain and tumor information by gene symbol simultaneously. Now, for example, a search of MTB using the gene symbol for the retinoblastoma 1 gene (Rb1) will return information both on the strains that carry a targeted, induced or spontaneous allele of the Rb1 gene, as

55、well as on the tumors that have reported genetic alterations (e.g.,point mutations, deletions, etc.) in the Rb1 gene. The query results for gene symbol searches are returned in two parts. First, a list of the alleles for genes represented in MTB is returned. Second, the associations of the alleles w

56、ith either tumor and/or strains are indicated along with hypertext links to the appropriate detail pages. Enhancements to the tumor frequency gridThe MTB tumor frequency grid was introduced in 1999 as a graphical means of querying and displaying complex cancer profile information for families of inb

57、red strains of mice ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C5#GKE019C5 5). The tumor frequency grid includes most of the inbred strains of mice that are being systematically characterized as part of an international collaboration (also known as the mouse phenome project) to establish broad ba

58、seline phenotypic data on commonly used and genetically diverse inbred strains of the laboratory mouse ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C10#GKE019C10 10). We have made two enhancements to the tumor frequency grid to make it more informative for our users. First, we changed the grid from

59、 a three-color coding system to reflect tumor frequency to a five-color system. The display of five colors allows more precise information about tumor frequency to be communicated graphically and has the additional benefit that relative frequencies can be discerned even if the grid is printed out or

60、 displayed in black and white. Second, we re-structured the listing of the strains in the grid from an alphabetical order to groupings that are associated with the genealogical relationships of the inbred strains ( HYPERLINK /cgi/content/full/29/1/95 l GKE019C11#GKE019C11 11). This organization make