- Summary: Recent technological advancements enable measuring the binding of a transcription factor to thousands of DNA sequences, in order to infer its binding preferences. High-throughput-SELEX measures protein-DNA binding by deep sequencing over several cycles of enrichment. We devised a new algorithm called HTS-IBIS for the inference task. HTS-IBIS corrects for technological biases, selects the cycle and k, and builds a motif starting from a consensus k-mer in that cycle. In large scale tests, HTS-IBIS outperformed the extant automatic algorithm for the motif finding task on both in vitro and in vivo binding prediction. Availability: HTS-IBIS is available on acgt.cs.tau.ac.il/HTS-IBIS.