Apollo: A Sequencing-Technology-Independent, Scalable, and Accurate Assembly Polishing Algorithm

Can Firtina, Jeremie S. Kim, Mohammed Alser, Damla Senol Cali, A. Ercument Cicek, Can Alkan, Onur Mutlu

A large proportion of the basepairs in the long reads that third-generation sequencing technologies produce possess sequencing errors. These errors propagate to the assembly and affect the accuracy of genome analysis. Assembly polishing algorithms minimize error propagation by polishing or fixing errors in the assembly by using information from alignments between reads and the assembly (i.e., read-to-assembly alignment). However, current assembly polishing algorithms can only polish an assembly using reads either from a certain sequencing technology or from a small genome. This technology and genome-size dependency prevents assembly polishing algorithms from either (1) using all the available read sets from multiple sequencing technologies or (2) polishing large genomes. We introduce Apollo, a new assembly polishing algorithm that can 1) scale to polish assemblies of large genomes and 2) use multiple sets of reads from any sequencing technology to polish an assembly. Our goal is to provide a single algorithm that uses read sets from all sequencing technologies to polish assemblies and that can polish large genomes. Apollo 1) models an assembly as a profile hidden Markov model (pHMM), 2) uses read-to-assembly alignment to train the pHMM with the Forward-Backward algorithm, and 3) decodes the trained model with the Viterbi algorithm to produce a polished assembly. Our experiments with real read sets demonstrate that 1) Apollo is the only algorithm that can use reads from multiple sequencing technology within a single run and that can polish an assembly of any size, 2) using reads from multiple sequencing technologies produces a more accurate assembly compared to using reads from a single sequencing technology, and 3) Apollo performs better than or comparable to the state-of-the-art algorithms in terms of accuracy even when using reads from a single sequencing technology.

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