human hTERT-RPE1 cell line Raw sequence reads

We performed a platform for the unbiased identification of functional serine (S), threonine (T), and tyrosine (Y) at a genome-wide scale, which is highly relevant with phosphorylation. Using CRISPR-dependent adenine base editor (ABEmax) with iBAR strategy, we designed 817,089 single guide RNAs (sgRNAs) library predicted to perturb 584,337 S/T/Y at endogenous loci. We obtained 3,467 functional mutations contributing to cell fitness growth, most of them taken a high fraction exhibited phenotypes not found in relative gene knockout (KO). Two novel gain of function (GOF) mutants (Y130H and S194P) of MAP2K1 we characterized, could lead to a strong cell growth promotion. Additionally, the essentiality of disordered polyS region in human proteome emerged from our screens, which highlighted its unexplored role for cell fitness. Moreover, the enriched screening hits shown in patient-derived samples, were observed in our data, indicative of potential cancer driver mutations.