a comprehensive benchmark study of multiple sequence alignment methods current challenges and future perspectives综合基准多重序列比对方法研究当前的挑战和未来的观点.pdfVIP

A Comprehensive Benchmark Study of Multiple Sequence Alignment Methods: Current Challenges and Future Perspectives Julie D. Thompson*, Benjamin Linard, Odile Lecompte, Olivier Poch ´ ´ ´ ´ ´ ´ Departement de Biologie Structurale et Genomique, IGBMC (Institut de Genetique et de Biologie Moleculaire et Cellulaire), CNRS/INSERM/Universite de Strasbourg, Illkirch, France Abstract Multiple comparison or alignmentof protein sequences has become a fundamental tool in many different domains in modern molecular biology, from evolutionary studies to prediction of 2D/3D structure, molecular function and inter- molecular interactions etc. By placing the sequence in the framework of the overall family, multiple alignments can be used to identify conserved features and to highlight differences or specificities. In this paper, we describe a comprehensive evaluation of many of the most popular methods for multiple sequence alignment (MSA), based on a new benchmark test set. The benchmark is designed to represent typical problems encountered when aligning the large protein sequence sets that result from today’s high throughput biotechnologies. We show that alignmentmethods have significantly progressed and can now identify most of the shared sequence features that determine the broad molecular function(s) of a protein family, even for divergent sequences. However,we have identified a number of important challenges. First, the locally conserved regions, that reflect functional specificities or that modulate a protein’s function in a given cellular context,are less well aligned. Second, motifs in natively disordered regions are often misaligned. Third, the badly predicted or