11,607 research outputs found
Accurate De Novo Prediction of Protein Contact Map by Ultra-Deep Learning Model
Recently exciting progress has been made on protein contact prediction, but
the predicted contacts for proteins without many sequence homologs is still of
low quality and not very useful for de novo structure prediction. This paper
presents a new deep learning method that predicts contacts by integrating both
evolutionary coupling (EC) and sequence conservation information through an
ultra-deep neural network formed by two deep residual networks. This deep
neural network allows us to model very complex sequence-contact relationship as
well as long-range inter-contact correlation. Our method greatly outperforms
existing contact prediction methods and leads to much more accurate
contact-assisted protein folding. Tested on three datasets of 579 proteins, the
average top L long-range prediction accuracy obtained our method, the
representative EC method CCMpred and the CASP11 winner MetaPSICOV is 0.47, 0.21
and 0.30, respectively; the average top L/10 long-range accuracy of our method,
CCMpred and MetaPSICOV is 0.77, 0.47 and 0.59, respectively. Ab initio folding
using our predicted contacts as restraints can yield correct folds (i.e.,
TMscore>0.6) for 203 test proteins, while that using MetaPSICOV- and
CCMpred-predicted contacts can do so for only 79 and 62 proteins, respectively.
Further, our contact-assisted models have much better quality than
template-based models. Using our predicted contacts as restraints, we can (ab
initio) fold 208 of the 398 membrane proteins with TMscore>0.5. By contrast,
when the training proteins of our method are used as templates, homology
modeling can only do so for 10 of them. One interesting finding is that even if
we do not train our prediction models with any membrane proteins, our method
works very well on membrane protein prediction. Finally, in recent blind CAMEO
benchmark our method successfully folded 5 test proteins with a novel fold
Kernel methods in genomics and computational biology
Support vector machines and kernel methods are increasingly popular in
genomics and computational biology, due to their good performance in real-world
applications and strong modularity that makes them suitable to a wide range of
problems, from the classification of tumors to the automatic annotation of
proteins. Their ability to work in high dimension, to process non-vectorial
data, and the natural framework they provide to integrate heterogeneous data
are particularly relevant to various problems arising in computational biology.
In this chapter we survey some of the most prominent applications published so
far, highlighting the particular developments in kernel methods triggered by
problems in biology, and mention a few promising research directions likely to
expand in the future
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