1. Browse to the file contains the miR data; the file should contain only the expression data such that each row is a miR and each column is a sample. <example>

2. Browse to the file contains the miR names corresponding to the miR data file. <example>

3. Browse to the file contains the mRNA data; the file should contain only the expression data such that each row is a gene and each column is a sample. The order of the samples (columns) should be the same as in the miR data file. <example>

4. Browse to the file contains the official gene symbol names corresponding to the mRNA data file. <example>

--- NOTE: the expression data files of the miR and mRNA data should contain only numbers without NA or Null values ---

5. Select the sequence-based prediction algorithm to use.

6. Select the species

7. Select whether you would like to perform a short run; if yes – check this box.

The p-value is calculated based on a random model, and the reproducibility of it is depending on the number of permutations. In the short run there are fewer permutations and therefore the p-values are less stable and might change a bit in different runs.

8. Browse to the directory in which you would like to save the output files.

9. Choose a name for CoSMic results file.

10. Run your analysis. When CoSMic finishes your analysis a message will appear on the screen.

CoSMic’s output files:

1. run_params.txt – A parameter file containing the selected species, prediction algorithm and whether the short run option was selected (1 if yes, 0 if not).

2. list_of_mirs_in_sb_prediction_file.txt – Names of miRs appear in the selected sequence-based predictions.

3. mirs_found_in_sb_predictions.txt - Names of miRs, inserted by the user in the miR names file, that were found in the sequence-based predictions.

4. mirs_missing_in_sb_predictions.txt - Names of miRs, inserted by the user in the miR names file, that were not found in the sequence-based predictions.

Note that due to rapid changing in the miR names convention, the same miR (i.e. sequence) has sometimes different names (for example miR-122a in the old version of Agilent array is miR-122 in the current miRBase version). If a situation like this revealed, the user can change the name of the missing miR in the miR names file to be the same as it appears in the sequence-based predictions.

5. <output_file>.txt – Contains the CoSMic results in the following format:

Column A: miR names

Column B: The p-value each miR obtained for the enrichment of the group of anti-correlated genes in the group of predicted target genes (After the random model).

Column C: The q-value each miR obtained for the enrichment of the group of anti-correlated genes in the group of predicted target genes (After the random model).

Column D: The number of target genes identified by CoSMic as functional and context specific for the corresponding miR (at the negative correlation procedure).

Column E: The names of the target genes identified by CoSMic as functional and context specific for the corresponding miR (at the negative correlation procedure).

Column F: The p-value each miR obtained for the enrichment of the group of correlated genes in the group of predicted target genes (After the random model).

Column G: The q-value each miR obtained for the enrichment of the group of correlated genes in the group of predicted target genes (After the random model).

Column H: The number of target genes identified by CoSMic as functional and context specific for the corresponding miR (at the positive correlation procedure).

Column I: The names of the target genes identified by CoSMic as functional and context specific for the corresponding miR (at the positive correlation procedure).