Recorded 27 February 2023. Xavier Bresson of the National University of Singapore presents "Learning to Untangle Genome Assembly Graphs" at IPAM's Artificial Intelligence and Discrete Optimization Workshop. Abstract: A quest to determine the complete sequence of a human DNA from telomere to telomere started three decades ago and was finally completed in 2021. This accomplishment was a result of a tremendous effort of numerous experts who engineered various tools and performed laborious manual inspection to achieve the first gapless genome sequence. However, such method can hardly be used as a general approach to assemble different genomes, especially when the assembly speed is critical given the large amount of data. In this work, we explore a different approach to the central part of the genome assembly task that consists of untangling a large assembly graph from which a genomic sequence needs to be reconstructed. Our main motivation is to reduce human-engineered heuristics and use deep learning to develop more generalizable reconstruction techniques. Precisely, we introduce a new learning framework to train a graph convolutional network to resolve assembly graphs by finding a correct path through them. The training is supervised with a dataset generated from the resolved CHM13 human sequence and tested on assembly graphs built using real human PacBio HiFi reads. Experimental results show that a model, trained on simulated graphs generated solely from a single chromosome, is able to remarkably resolve all other chromosomes. Moreover, the model outperforms hand-crafted heuristics from a state-of-the-art de novo assembler on the same graphs. Reconstructed chromosomes with graph networks are more accurate on nucleotide level, report lower number of contigs, higher genome reconstructed fraction and NG50/NGA50 assessment metrics. Learn more online at: http://www.ipam.ucla.edu/programs/workshops/artificial-intelligence-and-discrete-optimization/