Some of the computational methods he developed are considered pioneering work in areas such as biological text mining, protein coevolution, disease networks and more recently modelling cellular systems (digital twins).

[12][14] The 1994 paper "Correlated mutations and residue contacts in proteins",[15] of which Valencia was senior author, established the idea that correlated mutations at corresponding locations in the DNA sequences in different organisms could indicate that those locations corresponded to amino-acid residues that were physically close to each other in the final protein, informing the prediction of contact maps.

This previously unconsidered source of side information for protein structure prediction became used with increasing effectiveness in the 2010s, leading ultimately to the success of DeepMind's AlphaFold 2 algorithm in 2020.

[13] In 2006 he moved to the Spanish National Cancer Research Center (CNIO) as Director of the Structural Biology and Biocomputing programme.

All these actives converge into the general topic of Personalised Medicine, with particular interest in the interface with Artificial intelligence and High Performance Computing.

[11] He is currently co-executive editor of the journal Bioinformatics, and member of the Editorial boards of eLIFE, FEBS Letters, PeerJ and F1000 Prime.