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1、.:.;人類腫瘤的鼠模型網絡入口:鼠的腫瘤生物學數(shù)據(jù)庫生命科學學院2002級生物技術 曹文瑞 學號:021402153摘要鼠的腫瘤生物學數(shù)據(jù)庫MTB提供有遺傳詳細闡明(即先天性,轉基因和有目的的突變種)的老鼠種群腫瘤遺傳學和病理學的詳細信息資源。這個數(shù)據(jù)庫中的數(shù)據(jù)資源包括曾經發(fā)表的科學文獻以及科學團體的直接的數(shù)據(jù)論據(jù)。研討者利用基于環(huán)球網的訊問窗體訪問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?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。鼠的腫瘤生物學數(shù)據(jù)庫自
2、1998年在鼠基因組信息學網站( HYPERLINK )上提供運用。最近我們對MTB進展了一些改良,包括新的查詢選項、重新設計的查詢窗體和病理學及遺傳學數(shù)據(jù)的結果界面、添加了病理學數(shù)據(jù)的電子數(shù)據(jù)論據(jù)和注解工具。導言實驗室中老鼠曾經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展改造、易于實驗操作??梢源_切的反映人類癌癥和組織病理學的發(fā)育中的鼠模型是1998年由國家癌癥學會一次“偶爾的時機發(fā)現(xiàn)的。鼠模型提供了探求疾病進展過程中遺傳及細胞方面的變化以及對有能夠運用于臨床的治療戰(zhàn)略進展測試的手段。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基因或靶突變的適宜鼠種系是重要的。許多關于有遺傳詳細闡明(即先天性,轉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基因或定點突變鼠品系癌癥方式的方式下是不可用的。將連成一體的關于有遺傳詳細闡明的鼠品系遺傳和病理生物學的不同數(shù)據(jù)放入一個可查詢的數(shù)據(jù)庫是MTB第一位的義務。在最近的一項對腫瘤遺傳學研討的網絡資源的調
4、查中,我們發(fā)現(xiàn)了70余個與根底腫瘤遺傳學研討相關的數(shù)據(jù)庫和信息資源。大多數(shù)現(xiàn)有腫瘤相關資源和數(shù)據(jù)庫集中于單個基因或特殊的腫瘤性狀。在我們調查的站點中,僅有少數(shù)提供關于人腫瘤鼠模型的信息;提供實驗室老鼠病理生物學詳細信息的站點那么更少。在提供有關腫瘤遺傳學和病理學的綜合數(shù)據(jù)的范圍和深度上,MTB在現(xiàn)有的資源中是獨一無二的。MTB自1998年以來就可以經過環(huán)球網方便的運用。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、病理學和參考文獻已發(fā)表和未發(fā)表的文獻都包含于這個數(shù)據(jù)庫中。這些方面代表了查詢此數(shù)據(jù)庫的基于網絡的窗體的主要內容。MTB是用于描畫由Jackson實驗室鼠基因組信息MGI組織建
5、立的實驗室老鼠品系遺傳及生物學信息的信息學下部構造的延伸。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)庫中運用的解剖學術語于基因表達數(shù)據(jù)庫GXD鼠解剖學控制性詞匯。MTB中的許多病理學和診斷學術語于一本權威的教科書衰老鼠的病理學。2000年對MTB的改良關于MTB的設計和實施細節(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)庫運用者的最普遍的意見是提供額外的查詢選項和對病理學及遺傳學數(shù)據(jù)的報道。運用者還要求我們重新設計一些數(shù)據(jù)摘要頁面以便使他們
6、不用經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)的改動細節(jié)將在下面進展闡明。對這些變化進展闡明的網絡鏈接可以在本文的在線版本中看到增補資料。腫瘤類型查詢的新查詢選項我們實現(xiàn)了對腫瘤類型查詢選項兩個方面的改良。首先,我們添加了經過解剖學體系而不僅僅是器官稱號查詢數(shù)據(jù)庫的才干。運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。對病理學查詢的改良在早先的MTB版本中,運用者可以僅僅查詢和查看特殊的種/腫瘤結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數(shù)據(jù)搜索病理學數(shù)據(jù)。經過這項改良,數(shù)據(jù)庫運用者可以在MTB中經過一項查詢產生關于病理學數(shù)據(jù)廣泛查詢的結果而不用需一次找一個腫瘤/品系組合。MTB中對病理學數(shù)據(jù)陳說的第二項改良與對組織學圖像的顯示相關聯(lián)。在早先的數(shù)據(jù)庫版本中,運用者需求在病理學摘要頁面用鼠標點擊一個組織學圖像極小的版本來查看
8、一個對細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前窗口,運用者不能再對圖像和為圖像提供的診斷正文進展比較。我們實現(xiàn)了對這種進退兩難的局面的簡單處理方法,運用者可以經過用鼠標點擊一個位于極小版本的顯微圖片下方的標有“查看更大圖片的按鈕在一個獨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立窗口可以調整大小、可以獨立于網站主頁而封鎖。對基因查詢的改良在MTB數(shù)據(jù)庫的概念和邏輯設計中,我們過去把腫瘤細胞中遺傳改動的概念從與某一特定品系老鼠的背景相關的遺傳學中分別出來。結果,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展搜索
9、。我們實現(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)生遺傳改動如點突變,缺失等的腫瘤的信息?;蚍柕牟樵兘Y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)絡會連同適當詳細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)作為以建立通常運用和遺傳上多樣的實驗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展了重新構造,使它們由以字母順序排序變?yōu)橐约兿抵甑南底V關系分組。這種組織方式使尋覓預期在腫瘤易感性方式比較類似的種系。病理學信息的電子數(shù)據(jù)論據(jù):JaxPathMTB最初獲得信息的方式是經過腫瘤生物學和鼠遺傳學方面的專家級生
11、物學家對已發(fā)表科學文獻的進展定期回想。為了給病理學信息提供電子論據(jù)和共有的查詢方法,我們發(fā)明了一個從MTB主頁容易進入的基于網絡的數(shù)據(jù)庫JaxPath。JaxPath允許用戶向MTB提交未發(fā)表的病理學圖像和數(shù)據(jù),或者或者添加由于空間或費用緣由而沒有包含于初始發(fā)表文章之內的增補圖像。向JaxPath提交數(shù)據(jù)的運用者會被分配一個允許他們經過網絡對投稿的闡明和注解進展編輯的密碼。對投稿者圖片和注解的援用會在網站的病理學數(shù)據(jù)摘要中顯示。利用MTB進展查詢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)庫中每一腫瘤的實例都以腫瘤稱號、品系、性別和腫瘤來源器官的組合進展描畫的。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)揚重要作用的根本想象。MTB中每一腫瘤實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)定鏈接的標識符這些添加的標識符在許多查詢結果頁面中顯示中。曾經在他們感興趣經過常規(guī)方法進展查詢的數(shù)據(jù)庫中鑒別出特定記錄的運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語一致命名法的機構。MMHCC正在建造一個將包括關于治療藥物檢測和在MTB范圍以外的實驗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向詳細記述的臨床前和臨床鼠模型、實驗草案和治療實驗結果。參考文獻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
14、f?access_num=7585036&link_type=MED Medline 2 DePinho,R.A. and Jacks,T. (1999) Mouse models of cancer: Introductory comments. Oncogene, 18, 5248. HYPERLINK /cgi/external_ref?access_num=000082808400001&link_type=ISI ISI 3 Klausner,R. (1999) Studying cancer in the mouse. Oncogene, 18, 52495252. HYPERLI
15、NK /cgi/external_ref?access_num=000082808400002&link_type=ISI ISI HYPERLINK /cgi/external_ref?access_num=10498876&link_type=MED Medline 4 Bult,C.J., Krupke,D.M. and Eppig,J.T. (1999) Electronic access to mouse tumor data: the Mouse Tumor Biology Database (MTB) project. NucleicAcids Res., 27, 99105.
16、HYPERLINK /cgi/ijlink?linkType=ABST&journalCode=nar&resid=27/1/99 Abstract/Free FullText 5 Bult,C.J., Krupke,D.M., Sundberg,J.P. and Eppig,J.T. (2000) Mouse Tumor Biology Database (MTB): enhancements and current status. Nucleic Acids Res., 28, 112114. HYPERLINK /cgi/ijlink?linkType=ABST&journalCode=
17、nar&resid=28/1/112 Abstract/Free FullText 6 Bult,C.J., Krupke,D.M., Tennent,B.J. and Eppig,J.T. (1999) A survey of web resources for basic cancer genetics research. Genome Res., 9, 397408. HYPERLINK /cgi/ijlink?linkType=FULL&journalCode=genome&resid=9/5/397 Free FullText 7 Blake,J.A., Eppig,J.T., Ri
18、chardson,J.E., Kadin,J.A., Bult,C.J. and the Mouse Genome Database Group. (2001) The Mouse Genome Database (MGD): Integration Nexus for the Laboratory Mouse. Nucleic Acids Res., 29, 9194. HYPERLINK /cgi/ijlink?linkType=ABST&journalCode=nar&resid=29/1/91 Abstract/Free FullText 8 Ringwald,M., Eppig,J.
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
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