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Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. In recent years, hundreds of TFs have been characterized using high-throughput in vitro DNA binding assays coupled with deep sequencing. Variations of these assays can characterize binding by TF complexes and by RNA-binding proteins, or binding to chemically modified DNA. However, no unified method for analyzing all these data yet exists. We recently developed an algorithm named No Read Left Behind or NRLB (Rastogi et al., PNAS, 2018), which infers biophysical binding specificity models across the full affinity range from single-round SELEX data. It predicts human MAX homodimer binding in near-perfect agreement with existing low-throughput measurements, captures the specificity of the full-length p53 tetramer, and distinguishes multiple binding modes within a single sample. In addition to …