T-Coffee is a multiple sequence alignment software using a progressive approach. It generates a library of pairwise alignments to guide the multiple sequence alignment. It can also combine multiple sequences alignments obtained previously and in the latest versions can use structural information from PDB files. It has advanced features to evaluate the quality of the alignments and some capacity for identifying occurrence of motifs. It produces alignment in the aln format by default, but can also producePIR, MSF, and FASTA format. The most common input formats are supported.
Comparisons with other alignment software
While the default output is a Clustal-like format, it is sufficiently different from the output of ClustalW/X that many programs supporting Clustal format cannot read it; fortunately ClustalX canimport T-Coffee output so the simplest fix for this issue is usually to import T-Coffee's output into ClustalX and then re-export. Another possibility is to request the strict Clustalw output format with the option "-output=clustalw_aln". An important specificity of T-Coffee is its ability to combine different methods and different data types. In its latest version, T-Coffee can be used to combine protein sequences and structures, RNA sequences and structures. It can also run and combine the output of the most common sequence and structure alignment packages. For a complete list see: T-Coffee comes along with a sophisticated sequence reformatting utility named seq_reformat. An extensive documentation is available from along with a tutorial
Variations
;M-Coffee : a special mode of T-Coffee that makes it possible to combine the output of the most common multiplesequence alignment packages. The resulting alignments are slightly better than the individual one, but most importantly the program indicates the alignment regions where the various packages agree upon. Regions of high agreement are usually well aligned. ;Expresso and 3D-Coffee : these are special modes of T-Coffee making it possible to combine sequence and structures in an alignment. The structure based alignments can be carried out using the most common structural aligners such as TMalign, Mustang, and sap. ;R-Coffee : a special mode of T-Coffee making it possible to align RNA sequences while using secondary structure information. ;PSI-Coffee : aligns distantly related proteins using homology extension ;TM-Coffee : aligns transmembrane proteins using homology extension ;Pro-Coffee : aligns homologous promoter regions ;Accurate : automatically combine the most accurate modes for DNA, RNA and proteins ;Combine : combines two multiple sequence alignments into a single one.
Evaluation
; : an extended version of the T-Coffee scoring scheme. It uses T-Coffee libraries of pairwise alignments to evaluate any third party MSA. Pairwise projections can be produced using fast or slow methods, thus allowing a trade-off between speed and accuracy. TCS has been shown to lead to significantly better estimates of structural accuracy and more accurate phylogenetic trees against Heads-or-Tails, GUIDANCE, Gblocks, and trimAl.
