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Accelerated Profile HMM Searches

Figure 1

The MSV profile.

A: Profile HMM architecture used by HMMER3 [4], [5], [31]. Regions homologously aligned to the query are represented by a linear core model consisting of consensus positions (in this example, ), each consisting of a match, a delete, and an insert state (shown as boxes marked M, circles marked D, and diamonds marked I), connected by state transition probabilities (arrows). Match states carry position-specific emission probabilities for scoring residues at each consensus position. Insert states emit residues with emission probabilities identical to a background distribution. Additional flanking states (marked N, C, and J) emit zero or more residues from the background distribution, modeling nonhomologous regions preceding, following, or joining homologous regions aligned to the core model. Start (S), begin (B), end (E) and termination (T) states do not emit. B: The MSV profile is formed by implicitly treating all match-match transition probabilities as 1.0. This corresponds to the virtual removal of the delete and insert states. The rest of the profile parameterization stays the same. This model generates sequences containing one or more ungapped local alignment segments. Note that both models appear to be improperly normalized; for example, each match state in the MSV model has probability 1.0 local exit transition (orange arrows) in addition to the probability 1.0 match-match transition. This is because of a trick used to establish a uniform local fragment length distribution, in which these profiles are collapsed representations of a much larger (and properly normalized) “implicit probability model”, as explained in [31]. C: An example of what an alignment of a larger MSV profile (of length ) to a target sequence (of length ) might look like, as a path through a dynamic programming (DP) matrix. Here, the model identifies two high-scoring ungapped alignment segments (black dots, indicating residues aligned to profile match states), and assigns all other residues to N, J, and C states in the model (orange dots; unfilled indicates a “mute” nonemitting state or state transition). Note that the ungapped diagonals are not enforced to be consistent with a single gapped alignment.

doi: https://doi.org/10.1371/journal.pcbi.1002195.g001