Accurately clustering biological sequences in linear time by relatedness sorting

Clustering biological sequences into similar groups is an increasingly important task as the number of available sequences continues to grow exponentially. Search-based approaches to clustering scale super-linearly with the number of input sequences, making it impractical to cluster very large sets of sequences. Approaches to clustering sequences in linear time currently lack the accuracy of super-linear approaches. Here, I set out to develop and characterize a strategy for clustering with linear time complexity that retains the accuracy of less scalable approaches. The resulting algorithm, named Clusterize, sorts sequences by relatedness to linearize the clustering problem. Clusterize produces clusters with accuracy rivaling popular programs (CD-HIT, MMseqs2, and UCLUST) but exhibits linear asymptotic scalability. Clusterize generates higher accuracy and oftentimes much larger clusters than Linclust, a fast linear time clustering algorithm. I demonstrate the utility of Clusterize by accurately solving different clustering problems involving millions of nucleotide or protein sequences.