GeneMark-ETP significantly improves the accuracy of automatic annotation of large eukaryotic genomes.

Large-scale genomic initiatives, such as the Earth BioGenome Project, require efficient methods for eukaryotic genome annotation. Here we present an automatic gene finder, GeneMark-ETP, integrating genomic-, transcriptomic-, and protein-derived evidence that has been developed with a focus on large plant and animal genomes. GeneMark-ETP first identifies genomic loci where extrinsic data are sufficient for making gene predictions with "high confidence." The genes situated in the genomic space between the high-confidence genes are predicted in the next stage. The set of high-confidence genes serves as an initial training set for the statistical model. Further on, the model parameters are iteratively updated in the rounds of gene prediction and parameter re-estimation. Upon reaching convergence, GeneMark-ETP makes the final predictions and delivers the whole complement of predicted genes. GeneMark-ETP outperforms gene finders using a single type of extrinsic evidence. Comparisons with gene finders MAKER2 and TSEBRA, those that use both transcript- and protein-derived extrinsic evidence, show that GeneMark-ETP delivers state-of-the-art gene-prediction accuracy, with the margin of outperforming existing approaches increasing in its application to larger and more complex eukaryotic genomes.