The problem How to integrate the massive amounts of data on Drosophila neurobiology to explore anatomy, formulate hypotheses and find reagents?

Behavior/neural process ontology on FlyBase Gene ontology annotations of genes – neurological system process 7,904 annotations coverring 3,099 proteins and 121 terms – behavior 1,964 annotations coverring 932 proteins and 89 terms Phenotypes – Number of annotations: 4961 – Number of terms used in annotation: 24 – all defined using GO. Gene ontology annotations of anatomical structures – neurological system process: 1479 detection of stimulus involved in sensory perception: 1467 – GO behavior: 17

Genetic dissection of neural circuit function transgenic driver(s) target expression to specific neuron classes repress neural activity activate modulate behavior direct assays of neural activity UAS - < some activity modulator > Mutant

Expresses Fru Scer\GAL4[fru-NP0021] Expresses DA1 vPN GO: response to pheromone GO: sensory perception of smell GO: male courtship behavior Function Phenotype Anatomical phenotypes

registration (warping) e.g.- neurons with some part in AMMC QUERIES computation of overlap 3D co-ordinates for neuron Neuron based bioinformatics: tracking 3D data 3D co-ordinates for Brain regions segmentation Standard brain => standard 3D coordinate space

Analysis of cross-registered 3 D image data Predicted innervation patterns NeuronBlast => predictions of neuron classes Predicted connectivity from Arbor proximity

300 µm / 40,000 neurons 3D overlap defines potential connectivity Output

300 µm / 40,000 neurons 3D overlap defines potential connectivity

Queries Neurons by function (inferred from phenotype or electrophysiology) Phenotypes due to modulation of neurons in expression domain of driver X Potential circuit partners – direct or indirect, with X function

Functional annotation using GO

What we need Clear definitions and safe inference – infer classification Avoid vertebrate specificity – references to anatomical structures – references to species specific movement types – Bundling together of functions in species specific ways (vestibulo-auditory) Cross ontology integration – GO; Uberon; CHEBI, PATO