  Increasing size of sequence databases caused by the development of high
throughput sequencing, poses multiple alignment algorithms to face one of the
greatest challenges yet. As we show, well-established techniques employed for
increasing alignment quality, i.e., refinement and consistency, are ineffective
when large protein families are of interest. We present QuickProbs 2, an
algorithm for multiple sequence alignment. Based on probabilistic models,
equipped with novel column-oriented refinement and selective consistency, it
offers outstanding accuracy. When analysing hundreds of sequences, QuickProbs 2
is significantly better than Clustal Omega, the previous leader for processing
numerous protein families. In the case of smaller sets, for which
consistency-based methods are the best performing, QuickProbs 2 is also
superior to the competitors. Due to computational scalability of selective
consistency and utilisation of massively parallel architectures, presented
algorithm is comparable to Clustal Omega in terms of execution time, and orders
of magnitude faster than full consistency approaches, like MSAProbs or PicXAA.
All these make QuickProbs 2 a useful tool for aligning families ranging from
few, to hundreds of proteins. QuickProbs 2 is available at
https://github.com/refresh-bio/QuickProbs.
