Model-based analysis of competing-endogenous pathways (MACPath) in human cancers - Fig 3

<p><b>Identifying gained/lost indirect cePathway relationships (a).</b> In normal when regulating miRNAs (R1 and R2) are active (in abundance relative to other competing molecules[<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006074#pcbi.1006074.ref021" target="_blank">21</a>]), down-regulation of x would direct more copies of R1 to repress y. In turn, repressed y would direct R2 to repress z. Overall, ceRNA relationship on (<i>x</i>, <i>y</i>) and (<i>y</i>, <i>z</i>) would yield indirect ceRNA relationship on (<i>x</i>, <i>z</i>). In tumor when (<i>x</i>, <i>y</i>) lost ceRNA relationship possibly in association to inactivation of the regulating miRNAs, down-regulation of x would not repress y and z, representing the loss of not only direct ceRNA relationship in (<i>x</i>, <i>y</i>) and (<i>y</i>, <i>z</i>) but also indirect ceRNA relationship in (<i>x</i>, <i>z</i>). From normal and tumor condition, (<i>x</i>, <i>z</i>) would lose co-expression in tumors (Δρ<0) altogether with (<i>y</i>, <i>z</i>) and (<i>x</i>, <i>z</i>). <b>(b).</b> Accumulative distribution of co-expression (ρ) in direct and indirect ceRNA relationships (found in direct and indirect cePathway relationships) in normal samples, compared to the same number of random pairs (n = 5,000).</p