text: We present the first sub-quadratic time algorithm that with high probability correctly reconstructs phylogenetic trees for short sequences generated by a Markov model of evolution. Due to rapid expansion in sequence databases, such very fast algorithms are becoming necessary. Other fast heuristics have been developed for building trees from very large alignments (, and ), but they lack theoretical performance guarantees. Our new algorithm runs in @math time, where @math is an increasing function of an upper bound on the branch lengths in the phylogeny, the upper bound @math must be below @math , and @math for all @math . For phylogenies with very short branches, the running time of our algorithm is close to linear. For example, if all branch lengths correspond to a mutation probability of less than 0.02, the running time of our algorithm is roughly @math . Via a prototype and a sequence of large-scale experiments, we show that many large phylogenies can be reconstructed fast, without compromising reconstruction accuracy.
  @cite_16: 
  @cite_13: Recently, we have identified a randomized quartet phylogeny algorithm that has O(nlogn) runtime with high probability, which is asymptotically optimal. Our algorithm has high probability of returning the correct phylogeny when quartet errors are independent and occur with known probability, and when the algorithm uses a guide tree on O(loglogn) taxa that is correct with high probability. In practice, none of these assumptions is correct: quartet errors are positively correlated and occur with unknown probability, and the guide tree is often error prone. Here, we bring our work out of the purely theoretical setting. We present a variety of extensions which, while only slowing the algorithm down by a constant factor, make its performance nearly comparable to that of Neighbour Joining , which requires Θ(n3) runtime in existing implementations. Our results suggest a new direction for quartet-based phylogenetic reconstruction that may yield striking speed improvements at minimal accuracy cost. An early prototype implementation of our software is available at http: www.cs.uwaterloo.ca jmtruszk qtree.tar.gz.
  @cite_12: Gene families are growing rapidly, but standard methods for inferring phylogenies do not scale to alignments with over 10,000 sequences. We present FastTree, a method for constructing large phylogenies and for estimating their reliability. Instead of storing a distance matrix, FastTree stores sequence profiles of internal nodes in the tree. FastTree uses these profiles to implement Neighbor-Joining and uses heuristics to quickly identify candidate joins. FastTree then uses nearest neighbor interchanges to reduce the length of the tree. For an alignment with N sequences, L sites, and a different characters, a distance matrix requires O(N2) space and O(N2L) time, but FastTree requires just O(NLa + N) memory and O(Nlog (N)La) time. To estimate the tree's reliability, FastTree uses local bootstrapping, which gives another 100-fold speedup over a distance matrix. For example, FastTree computed a tree and support values for 158,022 distinct 16S ribosomal RNAs in 17 h and 2.4 GB of memory. Just computing pairwise Jukes–Cantor distances and storing them, without inferring a tree or bootstrapping, would require 17 h and 50 GB of memory. In simulations, FastTree was slightly more accurate than Neighbor-Joining, BIONJ, or FastME; on genuine alignments, FastTree's topologies had higher likelihoods. FastTree is available at http: microbesonline.org fasttree.
  @cite_2: Reconstructing the evolutionary history of a set of species is a fundamental problem in biology and methods for solving this problem are gaged based on two characteristics: accuracy and efficiency. Neighbor Joining (NJ) is a so-called distance-based method that, thanks to its good accuracy and speed, has been embraced by the phylogeny community. It takes the distances between n taxa and produces in @Q(n^3) time a phylogenetic tree, i.e., a tree which aims to describe the evolutionary history of the taxa. In addition to performing well in practice, the NJ algorithm has optimal reconstruction radius. The contribution of this paper is twofold: (1) we present an algorithm called Fast Neighbor Joining (FNJ) with optimal reconstruction radius and optimal run time complexity O(n^2) and (2) we present a greatly simplified proof for the correctness of NJ. Initial experiments show that FNJ in practice has almost the same accuracy as NJ, indicating that the property of optimal reconstruction radius has great importance to their good performance. Moreover, we show how improved running time can be achieved for computing the so-called correction formulas.
summary: In parallel to these theoretical results, many researchers have developed phylogeny reconstruction algorithms that can analyze alignments of tens, or even hundreds, of thousands of taxa. Fast Neighbour Joining @cite_2 runs in @math time and gives results similar to neighbour joining, which requires @math time. FastTree @cite_12 reconstructs phylogenies without computing the full distance matrix, which results in @math runtime. Our own recent algorithm, QTree @cite_13 @cite_16 , runs in @math time, using an incremental approach to building trees. No theoretical guarantees exist for the quality of solutions obtained from these fast algorithms, however, under realistic assumptions about the evolutionary model, for short sequences.