Abstract
Recovering brain connectivity from tract tracing data is an important computational problem in the neurosciences. Mesoscopic connectome reconstruction was previously formulated as a structured matrix regression problem (Harris et al. in Neural Information Processing Systems, 2016), but existing techniques do not scale to the whole-brain setting. The corresponding matrix equation is challenging to solve due to large scale, ill-conditioning, and a general form that lacks a convergent splitting. We propose a greedy low-rank algorithm for the connectome reconstruction problem in very high dimensions. The algorithm approximates the solution by a sequence of rank-one updates which exploit the sparse and positive definite problem structure. This algorithm was described previously (Kressner and Sirković in Numer Lin Alg Appl 22(3):564-583, 2015) but never implemented for this connectome problem, leading to a number of challenges. We have had to design judicious stopping criteria and employ efficient solvers for the three main sub-problems of the algorithm, including an efficient GPU implementation that alleviates the main bottleneck for large datasets. The performance of the method is evaluated on three examples: an artificial "toy" dataset and two whole-cortex instances using data from the Allen Mouse Brain Connectivity Atlas. We find that the method is significantly faster than previous methods and that moderate ranks offer a good approximation. This speedup allows for the estimation of increasingly large-scale connectomes across taxa as these data become available from tracing experiments. The data and code are available online.