Thread by @pedrobeltrao

Thousands of phosphosites have been discovered with <5% having a known function. In our new preprint @d0choa uses a machine learning approach to address this gap

If you care what phosphosites may regulate your protein/process of interest read on

biorxiv.org/content/10.110…

with @AndrewJarnuczak and @juan_vizcaino we first reanalyzed most human phospho MS samples in @pride_ebi (~575 days elution time)

The varied samples gave us good coverage and the single MaxQuant run full control of FDR.

We found ~120k high confidence human phosphosites

@dochoa created the phosphosite functional score, integrating 59 features of functional relevance (e.g. conservation, regulation, structural features)

The score ranks human phosphosites according to their functional importance which we extensively validate (available in supp)

it can predict the consequence of genetic variation at phosphosite positions, which is also relevant to link disease causing mutations to kinase signaling mechanisms

With the help of many people @Cris_Vieitez @dlswaney some examples were experimentally tested. In one, Kyung-Min Noh's lab at EMBL showed how 2 phosphosites in SMARCC2 (SWI/SNF) may play a role in neuronal differentiation.

A lot of work goes into the features, including multiple previous projects of the group. the phylogenetic ages @RomainStuder , hotspots from Marta Strumillo, conditional regulation atlas @d0choa. kinase specificity models @DBradley_EBI and mutfunc calculations @omarwagih

Big thanks also to all of the proteomics researchers that deposit their data in public archives.