Signed motif analysis of the Caenorhabditis elegans neuronal network reveals positive feedforward and negative feedback loops

Nervous systems are complex biological networks with largely unknown structural and functional characteristics. Motif analysis is a robust tool that can reveal unique aspects of connectivity of a complex network. An ideal candidate for motif analysis is the connectome of the nematode Caenorhabditis elegans which is the only fully reconstructed nervous system. Utilizing recent data on the connection signs of this network and a novel structure-preserving randomization method, we performed signed motif analysis on the C. elegans connectome for the first time, to our knowledge. We identified 56 significantly over- and 1 underrepresented three-node signed motifs and revealed that certain motifs (e.g. positive feedforward, negative feedback, disinhibitory feedback, and incoherent feedforward loops) are overabundant in the C. elegans connectome. We further distinguished (coloured) nodes by corresponding neuron modalities (e.g. sensory vs. motor neurons) and found that there is characteristic neuronal layout for each significant feedforward and feedback loop. Our findings demonstrate the importance and potential of signed motif analysis in understanding biological networks. Our motif enumerating tool and definition system can be utilized in signed motif analysis of other complex networks.