A neural network method (SPINE-2D) is introduced to provide a sequence-based prediction of residue-residue contact maps. This method is built on the success of SPINE in predicting secondary structure, residue solvent accessibility, and backbone torsion angles via large-scale training with overfit protection and a twolayer neural network. SPINE- 2D achieved a 10-fold crossvalidated accuracy of 47% (62%) for top L/5 predicted contacts between two residues with sequence separation of six or more and an accuracy of 24 6 1% for nonlocal contacts with sequence separation of 24 residues or more. The accuracies of 23% and 26% for nonlocal contact predictions are achieved for two independent datasets of 500 proteins and 82 CASP 7 targets, respectively. A comparison with other methods indicates that SPINE-2D is among the most accurate methods for contact- map prediction.