MAGUS+eHMMs: improved multiple sequence alignment accuracy for fragmentary sequences

SUMMARY: Multiple sequence alignment is an initial step in many bioinformatics pipelines, including phylogeny estimation, protein structure prediction and taxonomic identification of reads produced in amplicon or metagenomic datasets, etc. Yet, alignment estimation is challenging on datasets that exhibit substantial sequence length heterogeneity, and especially when the datasets have fragmentary sequences as a result of including reads or contigs generated by next-generation sequencing technologies. Here, we examine techniques that have been developed to improve alignment estimation when datasets contain substantial numbers of fragmentary sequences. We find that MAGUS, a recently developed MSA method, is fairly robust to fragmentary sequences under many conditions, and that using a two-stage approach where MAGUS is used to align selected ‘backbone sequences’ and the remaining sequences are added into the alignment using ensembles of Hidden Markov Models further improves alignment accuracy. The combination of MAGUS with the ensemble of eHMMs (i.e. MAGUS+eHMMs) clearly improves on UPP, the previous leading method for aligning datasets with high levels of fragmentation. AVAILABILITY AND IMPLEMENTATION: UPP is available on https://github.com/smirarab/sepp, and MAGUS is available on https://github.com/vlasmirnov/MAGUS. MAGUS+eHMMs can be performed by running MAGUS to obtain the backbone alignment, and then using the backbone alignment as an input to UPP. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.