Copy Alterations Intuitive-Rendering Navigator
CAIRN: Copy Alterations Intuitive-Rendering Navigator
Purpose: To enable the user to quickly and easily graph all copy-number alterations (CNAs) present in a segment file. This could include deletions and amplifications in tumors, for example. Custom data is permitted, so users can be creative in their use of this tool.
Background: Cancer is not genetically different from normal cells in only one way. Single nucleotide changes, which can cause mutations to coding regions for proteins, are a widely researched source of somatic mutation which gives rise to cancer cells. However, an equally important mutation type is changes in copy numbers of genes. This occurs through deletions or amplifications of regions on a chromosome, via complex mechanisms. These CNAs can be very small – less than the length of a single gene – or entire chromosomes. One prevailing theory for why they exist in cancer is that deletions encompass many tumor suppressor genes and amplifications encompass many oncogenes. Hence, being able to view how many deletions or amplifications occur over a given region of DNA may be informative for how a particular cancer type manipulates its genome to drive tumor progression. If deletions and amplifications are roughly equal, that region is unlikely to affect tumor formation or progression. If deletions dominate, this cancer likely requires removal of tumor suppressors within that region of DNA. Similarly, if amplifications dominate the region, a tumor likely requires more copies of one or more oncogenes in the area for maximal proliferation.
With this tool, you can: -Display copy-number alterations (CNAs) which overlap a user specified region -Quantify the number of amplified CNAs and deleted CNAs
Options to modify your output include: -Use over 30 cancer types (online) -Use your own custom or downloaded segment dataset (an example is given) -Choose to display only deletions or only amplifications if desired -Query CNAs which end on a query region (for break points) -Query CNAs which overlap a query region (for gene-level CNAs) -Omit CNAs which also overlap another query region -Customize the definition of CNAs by strength and length -Display known oncogene and/or tumor suppressor locations -Overlay single nucleotide and short indel mutation oncogenic data when available -Customize the image size -Download the segments corresponding to your query
Explanation of inputs: Specify Cancer Type In the online version, mutltiple tumor types are preloaded into CAIRN. For the desktop app, segment files must be loaded into the “Segments” folder or uploaded into the custom file input section.
Or, upload custom CNA segment file (tab or comma delimited) Click to upload a custom CNA file for analysis. This overrides any “Specify Cancer Type” selection. Must be in hg19 coordinates for the original App. An example dataset can be found by clicking “Download example custom input data” or by finding the “Example_segments” file in the downloaded App.
Display segments which start/end near telomeres Will produce a graph of all segments which have at least one end ending within 2 megabases of the telomeres end points, as defined by hg19 coordinates.
Display only segments which start/end near centromeres Will produce a graph of all segments which have at least one end ending within 2 megabases of the centromere end points, as defined by hg19 coordinates.
Type of query Selects between a gene-based analysis or a coordinate-based analysis (ends or overlaps). Ends query regions where CNA break points overlap the query. Overlap queries CNAs which extend beyond both ends of the query region. Genes If genes are selected, type in the official gene symbol of your gene of interest. Note that many genes have many synonyms, so search for the official gene symbol if unknown (for example, on uniprot.org or Wikipedia) Force segments to also include genes (enter as: GENE1, GENE2) This enables you to search for co-deleted or co-amplified genes. Type in one or more extra official gene symbols for the query if desired Remove any segments containing gene This enables a search for segments which only include one gene but not another gene. This may help quantify if two genes are both tumor suppressors or if one may be an oncogene and one a tumor suppressor, when combined with other search data. Ends This is used to monitor where break sites may occur in a particular cancer type. Overlaps This can be used if a non-gene query is desired. Some examples may include chromosome arm coordinates, entire chromosome coordinates, microRNA locations, or repetitive DNA coordinates.
Run CAIRN This button will initiate a new calculation based on current input settings. It can also enable other graph labels to appear, but is not needed to resize the graph.
Minimum CNA amplitude Set the magnitude of segment data values which correspond to a deletion or amplification change. Typically, this is 0.2 for shallow deletions which may occur in only a subset of tumor cells. Higher values may enable searches for more stringent data, or for custom data segments with copy number calls (use 1).
Minimum CNA length (bp) The number of base-pairs in length each segment must be larger than to be displayed and counted.
Extend query region endpoints (bp) Enables searches which include some DNA upstream and downstream of a gene or region. Type in zero for a query which does not include any extension beyond the query region.
Label COSMIC tumor suppressor genes Labels genes which are annotated as tumor suppressors in COSMIC along the chromosome.
Label COSMIC oncogenes Labels genes which are annotated as oncogenes in COSMIC along the chromosome.
Mark mutant tumor suppressor genes on segments Additionally graphs triangle on any segment which contains a single nucleotide mutation or short indel of a COSMIC tumor suppressor gene on the query segments. Must click “Run CAIRN” to update the graph.
Mark mutant oncogenes on segments Additionally graphs a green triangle on any segment which contains a single nucleotide mutation or short indel of a COSMIC tumor suppressor gene on the query segments. Must click “Run CAIRN” to update the graph.
Plot only deletions Omits graphing of amplified regions.
Plot only amplifications Omits graphing of deleted regions.
Specify exact plot output size Check this box to specify the exact number of pixels you wish the graph to be.