TY - JOUR
T1 - Aligning biological sequences by exploiting residue conservation and coevolution
AU - Muntoni, Anna Paola
AU - Pagnani, Andrea
AU - Weigt, Martin
AU - Zamponi, Francesco
PY - 2020/12
Y1 - 2020/12
N2 - Sequences of nucleotides (for DNA and RNA) or amino acids (for proteins) are central objects in biology. Among the most important computational problems is that of sequence alignment, i.e., arranging sequences from different organisms in such a way to identify similar regions, to detect evolutionary relationships between sequences, and to predict biomolecular structure and function. This is typically addressed through profile models, which capture position specificities like conservation in sequences but assume an independent evolution of different positions. Over recent years, it has been well established that coevolution of different amino-acid positions is essential for maintaining three-dimensional structure and function. Modeling approaches based on inverse statistical physics can catch the coevolution signal in sequence ensembles, and they are now widely used in predicting protein structure, protein-protein interactions, and mutational landscapes. Here, we present DCAlign, an efficient alignment algorithm based on an approximate message-passing strategy, which is able to overcome the limitations of profile models, to include coevolution among positions in a general way, and to be therefore universally applicable to protein- and RNA-sequence alignment without the need of using complementary structural information. The potential of DCAlign is carefully explored using well-controlled simulated data, as well as real protein and RNA sequences.
AB - Sequences of nucleotides (for DNA and RNA) or amino acids (for proteins) are central objects in biology. Among the most important computational problems is that of sequence alignment, i.e., arranging sequences from different organisms in such a way to identify similar regions, to detect evolutionary relationships between sequences, and to predict biomolecular structure and function. This is typically addressed through profile models, which capture position specificities like conservation in sequences but assume an independent evolution of different positions. Over recent years, it has been well established that coevolution of different amino-acid positions is essential for maintaining three-dimensional structure and function. Modeling approaches based on inverse statistical physics can catch the coevolution signal in sequence ensembles, and they are now widely used in predicting protein structure, protein-protein interactions, and mutational landscapes. Here, we present DCAlign, an efficient alignment algorithm based on an approximate message-passing strategy, which is able to overcome the limitations of profile models, to include coevolution among positions in a general way, and to be therefore universally applicable to protein- and RNA-sequence alignment without the need of using complementary structural information. The potential of DCAlign is carefully explored using well-controlled simulated data, as well as real protein and RNA sequences.
U2 - 10.1103/PhysRevE.102.062409
DO - 10.1103/PhysRevE.102.062409
M3 - Article
C2 - 33465950
VL - 102
SP - 062409
JO - Physical Review E
JF - Physical Review E
SN - 1063-651X
IS - 6-1
ER -