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Sequences were chosen from the library 1 and library 2 based on differential expressions.
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All miRNAs selected based on differential expression were verified as markedly differentially expressed, with p-values varying from 10-7 to 10-21 and FC values up to 95 (Table 3).
As expected, both network-based ranking and ranking based on differential expression outperform random ranking.
For sets of 25 genes or more, network-based ranking outperforms ranking based on differential expression by covering more known disease genes, with up to three times higher coverage.
First, in contrast to other discretization-based methods such as SAMBA, ENIGMA discretizes the expression data based on differential expression p-values.
Genes were grouped by dynamics using an intersection of results based on differential expression analysis.
For example, although TP53 was first identified based on differential expression, it was soon thereafter found to be recurrently mutated in the majority of cancers25,27.
To identify significant microRNAs based on differential expression changes across time, we used significance analysis of microarrays method, adapted for small RNA-sequencing data (SAMSeq 41.
SAM analysis56 was used to rank genes based on differential expression scores, DAVID27 was used for GO-term analysis, and GSEA with C2, C6, and C7 gene lists was used for GSEA57.
Finally, it will be important to determine if the quiescent and proliferative beta-cells in zebrafish also differ in functionality, as reported for quiescent and proliferative mouse beta-cells based on differential expression of flat-top 18.
Based on differential expression and literature search, hsa-miR-135b was selected for further characterisation in different types of colonic polyps and cancer tissue.
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