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Practical Course on Multiple Sequence Alignment - CNB - Protein ...

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Choosing the right MSA software<br />

Given the multitude of choices, it can be difficult for a user of multiple<br />

alignment software to understand the situati<strong>on</strong>s in which a particular<br />

alignment tool is or is not appropriate. When aligning a small number (40%), most<br />

modern alignment programs will have no difficulty in returning a correct<br />

multiple sequence alignment, and no special c<strong>on</strong>siderati<strong>on</strong> is needed. When all<br />

of these c<strong>on</strong>diti<strong>on</strong>s do not hold, however, choosing the appropriate tools and<br />

c<strong>on</strong>figurati<strong>on</strong>, while keeping in mind the tradeoff between accuracy and<br />

computati<strong>on</strong>al cost, can be difficult. You can find a list of currently popular<br />

alignment software (see Table 2) and advice <strong>on</strong> tool selecti<strong>on</strong> (see Fig. 5).<br />

For more advanced discussi<strong>on</strong> <strong>on</strong> software selecti<strong>on</strong> see (Do & Katoh, 2008).<br />

Figure 5: Decisi<strong>on</strong> tree for choosing the right MSA program.<br />

<strong>Alignment</strong> visualizati<strong>on</strong> and editing<br />

Once an alignment has been generated, visualizati<strong>on</strong> tools allow manual<br />

identificati<strong>on</strong> of regi<strong>on</strong>s with reliably predicted homology; many of these tools<br />

also allow for interactive alignment editing.<br />

For alignments of sequences with low similarity, post-processing is extremely<br />

important as most regi<strong>on</strong>s in a low-identity alignment will not be reliably<br />

alignable.<br />

Visual inspecti<strong>on</strong> of an alignment and subsequent identificati<strong>on</strong> of potentially<br />

mis-aligned regi<strong>on</strong>s can be greatly helped using hints provided by software<br />

that highlight such regi<strong>on</strong>s. Typically, high c<strong>on</strong>fidence aligned regi<strong>on</strong>s can be<br />

identified by looking for groups of residues with str<strong>on</strong>gly c<strong>on</strong>served<br />

18

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