Updated project metadata. Sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. A subset of computationally predicted virulence factors was determined to be secreted into the host cytoplasm, and two of these, SrfN and PagK2, were required for full mouse virulence and defined a new class of translocated effectors involved in pathogenesis.