I've considered asking this question on [Bioinformatics SE][1], [Mathematics SE][2], and [Stats SE][3], however I've judged that my question belongs on Biology SE because I am interested in a biological (domain-specific) interpretation rather than a further development of the mathematics or software. My question pertains to applying graph theory to biology, so first I will describe the graph in its mathematical properties and how they reflect biological properties. ## The graph Let's consider a [weighted][4] and [directed][5] [graph][6] whose [nodes][7] represent [genes][8] and whose [edges][9] represent the [binary relation][10] *gene A [regulates][11] gene B*. The directionality of the edges is imposed in order to reflect that *gene A regulates gene B* does not imply that *gene B regulates gene A*. The [magnitudes][12] of the weights are to represent some measure of how "strongly" one gene is regulating another, and the [signs][13] of the weights are to represent whether the regulation is upregulation (positive) or downregulation (negative). For this graph, edges with a weight of zero are considered equivalent to 'no regulation' and should be excluded from the graph. # Path Analysis Restricting ourselves to [paths][14] that do not visit the same node twice, **what is the biological interpretation of the sum of the weights (of the edges) of a path between two nodes in the aforementioned graph?** I have conflicting intuitions. For example, why would these weights be additive? If they're not additive, then their summation is not necessarily meaningful. Conditioned on being meaningful in the first place, my other inuition is that the meaning of such a summation would reflect the strength of 'indirect' regulation [1]: https://bioinformatics.stackexchange.com/ [2]: https://math.stackexchange.com/ [3]: https://stats.stackexchange.com/ [4]: https://mathworld.wolfram.com/WeightedGraph.html [5]: https://en.wikipedia.org/wiki/Directed_graph [6]: https://en.wikipedia.org/wiki/Graph_(discrete_mathematics) [7]: https://en.wikipedia.org/wiki/Vertex_(graph_theory) [8]: https://en.wikipedia.org/wiki/Gene [9]: https://mathworld.wolfram.com/GraphEdge.html [10]: https://en.wikipedia.org/wiki/Binary_relation [11]: https://en.wikipedia.org/wiki/Regulation_of_gene_expression [12]: https://en.wikipedia.org/wiki/Magnitude_(mathematics) [13]: https://en.wikipedia.org/wiki/Sign_(mathematics) [14]: https://en.wikipedia.org/wiki/Path_(graph_theory)