Challenges in homology search: HMMER3 and convergent evolution of coiled-coil regions.
Challenges in homology search: HMMER3 and convergent evolution of coiled-coil regions.
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DOI：
10.1093/nar/gkt263
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发表时间：
2013-07
影响因子：
14.9
通讯作者：
Punta M
中科院分区：
文献类型：
--
作者：
Mistry J;Finn RD;Eddy SR;Bateman A;Punta M
通过序列相似性检测蛋白质同源性在生物学中具有重要的应用，从蛋白质结构和功能预测到系统发育的重建。尽管当前的对齐蛋白质序列的方法是强大的，但仍然存在挑战，包括同源过度扩展对齐的问题以及在收敛进化中的区域。在这里，我们测试了配置文件隐藏的Markov模型方法HMMER3将同源序列正确分配给PFAM数据库中> 13 000个手动策划的家庭的能力。我们使用蛋白质区域确定问题家族，这些蛋白质区域与PFAM相关的两个或多个尚未注释的PFAM家族匹配。我们发现，对于具有周期性偏见模式的家庭，例如在盘绕螺旋圈中通常观察到的HMMER3电子价值估计值似乎不太准确。这些结果支持在PFAM数据库中继续使用手动策划的包含阈值，尤其是在诸如此类实验中被确定为有问题的家庭的子集中。他们还强调了需要开发可以纠正这种特定类型的组成偏差的新方法的需求。
Detection of protein homology via sequence similarity has important applications in biology, from protein structure and function prediction to reconstruction of phylogenies. Although current methods for aligning protein sequences are powerful, challenges remain, including problems with homologous overextension of alignments and with regions under convergent evolution. Here, we test the ability of the profile hidden Markov model method HMMER3 to correctly assign homologous sequences to >13 000 manually curated families from the Pfam database. We identify problem families using protein regions that match two or more Pfam families not currently annotated as related in Pfam. We find that HMMER3 E-value estimates seem to be less accurate for families that feature periodic patterns of compositional bias, such as the ones typically observed in coiled-coils. These results support the continued use of manually curated inclusion thresholds in the Pfam database, especially on the subset of families that have been identified as problematic in experiments such as these. They also highlight the need for developing new methods that can correct for this particular type of compositional bias.
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