药物小分子cmap数据库—研究药物小分子、基因、疾病之间的关系

biostar

用途：用来研究药物小分子、基因、疾病之间的关系
访问地址：http://www.broadinstitute.org/cmap/

登陆帐户：
账号：www.biostatistic.net
密码：111111

简介:
   The Connectivity Map ,（也称为的cmap）是一个全基因组范围内利用生物活性的小分子来处理培养的人类细胞转录表达数据的收集,通过简单的匹配算法，使得研究药物分子、基因和疾病的关系成为了可能。
数据容量：
   目前的版本，包含大约1,309个化合物处理的7,000份表达谱。由于他们开发了自己的算法，因此生物学家，药理学家，化学家和临床科学不需要任何基因表达数据分析能力就能使用cmap数据库进行药物分子、基因、疾病的关系。

使用帮助：
You'll need a gene-expression signature to use cmap. To get you started, all newly-registered users have a typical query signature preloaded into their sandbox. This particular signature derives from a published gene-expression analysis of the effects of small-molecule histone deacetylase inhibitors (HDACi) in a number of human cell lines.

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To execute a query with this preloaded signature, first select the signature query page from the query tab found at the top of any page. Type a name for the result in the 'result name' field; choose any name you like. Click in the 'select a signature' field and select "HDACi (Glaser)"; this is the name we've given to the preloaded signature. Click 'execute query.'

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In about fifteen seconds a brief report of the query will be displayed. Take a look. Then, view the result by clicking 'view results now.' This will take you directly to the permuted result page with your result already selected. Alternatively, you can select 'permuted results' from the result tab at the top of the page, and click on the name you gave to your result in the 'select a result' dropdown menu.

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You'll see a page with a table displaying the twenty cmap perturbagens best 'connected' with your signature. Perturbagens with positive enrichment values are said to be more positively connected with your signature than any others in the collection. As you'd expect, these include some HDAC inhibitor (HDACi) compounds; vorinostat and trichostatin A, for example.

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Look at the individual instances that underlie the high ranking of these perturbagens. Click the little green, gray and red barview icon in the vorinostat row on the table. This will popup the result detail window showing the performance of all of the vorinostat instances with your signature, and a graphical representation of its connectivity, called a barview.

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Close the popup window and look at the table again. Another value of interest is specificity. Click the specificity value in the vorinostat row. This will popup the specificity popup. This window displays signatures to which vorinostat is better connected than your signature. As you'd anticipate, these are other HDACi signatures. Close the popup window.

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You can search for perturbagens that you're interested in. Begin typing "depudecin"--a structurally-distinct HDACi--in the textbox above the table and click on depudecin on the autocomplete menu. This will display the row for depudecin. It has a positive enrichment and a good permutation p-value, as you'd expect. Click the 'show all' button to take you back to the table.

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Detailed guidance on the interpretation of results is provided at how to interpret a result.

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You can find out more about the signature we preloaded for you by clicking on its name. This is found next to where it says 'signature:', under the dropdown menu. The signature popup will appear. As an exercise, download the two tag list files that represent this signature. Click on the file names immediately to the right of where it says 'up tags:' and 'down tags:' and save them to your desktop, making sure to give them a ".grp" file extension. Open them in a text editor or Excel and take a look at their structure. You'll see that genes are represented by probe sets from the cmap feature set.

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Now that you have two .grp files representing the up- and down- genes in a signature you can execute a query with the quick query page—this doesn't require that the signature be preloaded to your sandbox—or you can upload the signature to your sandbox using the load signature page and execute it using the signature query page as you did earlier. All of these pages are accessed through the query tab at the top of all pages.

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Go to the quick query page and browse to and select the two tag lists on your desktop in the fields labeled 'up tag list' and 'down tag list', and execute the query. You'll see a brief report about the query, as before. Click 'view results now', also as before. The result should be identical to the first one. You can switch between results simply by selecting a result name from the dropdown menu at the top of the page. Note that every result generated using the quick query page is given the name "temporary" and that it will be overwritten next time around.

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If you want to save your result you'll first need to save your signature using the load signature page. Navigate to that page and type a name into the 'title' textbox and a short description in the 'comment' textbox. Then upload your two tag lists as you did on the quick query page. Leave the supporting documentation fields empty and click the 'load signature' button. A report page will appear in a few seconds. You could execute a query with this new signature by clicking 'execute query with this signature' or you could go to the signature query page and select this signature from the dropdown, as you did earlier.

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Another source of signatures is the cmap data itself. The instance query page allows you to build a signature from a number of different instances on the fly, and then execute a query with this new so-called cmap signature. Go to the instance query page which can be found under the query tab at the top of all pages. Select the three instances of scriptaid—yet another HDACi—by typing "scriptaid" in the textbox, and using the autocomplete menu and the 'select this instance' buttons. Then select a threshold for gene selection by typing amplitude values in the textboxes labeled 'up threshold' and 'down threshold'; let's use "1" and "-1", respectively. Click the 'check tags' button to see how many probe sets pass these threshold values and click 'execute query.' As before, a brief description of the query will be displayed.

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Navigate to the permuted result page and take a look at your new result. All results from the instance query page are named "temporary" too, just like those from the quick query page, and your earlier result has been overwritten, as expected.

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Looking at this new 'temporary' result you'll see that scriptaid is now the top-ranked perturbagen. This is just what you'd expect when you use the three scriptaid instances to create the internal signature. Also, as expected, the top of the list is populated with the HDACi compounds we've seen before; vorinostat and trichostatin A.

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That's the end of the 'getting started' tutorial. Much more information and a detailed description of cmap terms and tools can be accessed by clicking 'topics' under the help tab, found at the top of all pages. You may also contact us with questions that our online help pages don't answer.