Once a profile HMM is loaded, HMMEditor is able to visualize it in the traditional layout view (Figure 2), HMM Logo view and HMM text view. It also can visualize the corresponding null model.

HMM layout view shows the structure of a profile HMM. The thickness of the transition line is proportional to the probability of the transition. The thickness of a border of an M state indicates the level of conservation. The label of each matching state denotes the most probable (consensus) residue emitted from the state.

Inside layout view, user can zoom in and zoom out the view and drag any node to get a better appearance. The layout view can be saved as a JPG or PNG file.

HMM text view shows the profile HMM in text view. The format of the text view is the same as HMMer. HMM text view is dynamically associated with the layout view. If a user edits profile HMM in the layout view, the changes will reflect in HMM text view instantly.

HMMer saves a profile HMM model into a text file, in which all the probabilities are converted into log-odds scores. Log-odds scores are not as intuitive as probabilities, making it hard for users to edit the model. HMMEditor provide the function to visually modify the structure and probability parameters of a profile HMM. To our best knowledge, it is the only tool equipped with this function. Figure 3 shows the interface to add, remove a state and to modify its transition and emission probabilities. User can select a state using mouse and click the right mouse button to pop up the editing menu. The delete menu lets user delete the matching state and the associated insertion and deletion states. The duplicate menu lets user to add an identical set M, I, D states before or after the current state. The modify menu allows user to modify the emission probabilities of M and I states and the transition probabilities of I, M and D states. Figures 4 and 5 show the dialogs of editing the transition and emission probabilities. Once a probability is modified, all other views will be updated immediately.

HMMEV provides a novel function to visualize the Viterbi (or optimal) path of aligning a sequence against a profile HMM using Viterbi algorithm. Figure 6 shows an example of aligning a short sequence “MDPHE” against a profile HMM consisting of five states. The visualization of Viterbi path help user see the conservation, deletion, and insertion of the sequence with respect the HMM of a family of sequence.

HMMEditor can read the sequence file in many popular formats such as FASTA and ClustalW 15. Once sequences are loaded into HMMEditor, user can view the Viterbi path of each sequence. Furthermore, use can edit a sequence, i.e. add or remove residues to see how the path changes. This provides a useful means for user to adjust sequence alignments manually.

User can also align multiple sequences against a profile HMM into multiple sequence alignment and save it into a file from HMMEditor, just as hmmalign does.

HMM Logo (Figure 7) 11 is a way to visualize a profile HMM, similarly as the popular motif logo used to visualize DNA binding sites 12. Figure 7 is an HMM logo generated by HMMEditor. A HMM Logo consists of a serial of character stacks (column) separated by light red lines. Each stack represents a matching state. The lines separating neighboring stacks represent an insertion state. The height of the stack shows how significantly the emission probability of a matching state deviates from the background emission probability, i.e relative entropy (or information content). Internally, the height of each character is proportional to its information content. The width of each stack or line is determined by the hitting probability of its corresponding state. Hitting probability is the probability that a path goes through the state, which is computed efficiently using dynamic programming algorithm as in 11. A narrow stack indicates that the state is less likely to be visited in a path. A narrow stack of a matching state means that the state is likely to be deleted instead of being visited in a path.