### Computational identification of cooperative transcription factor pairs

Four simple algorithms, which aim to investigate whether the performance of computational identification of cooperative TF pairs could be improved by using a more biologically relevant way to define the targets of a TF. Each algorithms consist of two steps. (Step 1) Define the targets of a TF using (i) ChIP-chip data in the first algorithm, (ii) TF binding data in the second algorithm, (iii) TF perturbation data in the third algorithm, and (iv) the intersection of TF binding and TF perturbation data in the fourth algorithm. Compared with the first three algorithms, the fourth algorithm uses a more biologically relevant way to define the targets of a TF. (Step 2) Measure the cooperativity of a TF pair by the statistical significance of the overlap of the targets of these two TFs using the hypergeometric test. By adopting four existing performance indices, we show that the fourth proposed algorithm (PA4) significantly outperforms the other three proposed algorithms. This suggests that the computational identification of cooperative TF pairs is indeed improved when using a more biologically relevant way to define the targets of a TF.