Heinzinger, Michael;
Littmann, Maria;
Sillitoe, Ian;
Bordin, Nicola;
Orengo, Christine;
Rost, Burkhard;
(2022)
Contrastive learning on protein embeddings enlightens midnight zone.
NAR Genomics and Bioinformatics
, 4
(2)
, Article lqac043. 10.1093/nargab/lqac043.
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Abstract
Experimental structures are leveraged through multiple sequence alignments, or more generally through homology-based inference (HBI), facilitating the transfer of information from a protein with known annotation to a query without any annotation. A recent alternative expands the concept of HBI from sequence-distance lookup to embedding-based annotation transfer (EAT). These embeddings are derived from protein Language Models (pLMs). Here, we introduce using single protein representations from pLMs for contrastive learning. This learning procedure creates a new set of embeddings that optimizes constraints captured by hierarchical classifications of protein 3D structures defined by the CATH resource. The approach, dubbed ProtTucker, has an improved ability to recognize distant homologous relationships than more traditional techniques such as threading or fold recognition. Thus, these embeddings have allowed sequence comparison to step into the 'midnight zone' of protein similarity, i.e. the region in which distantly related sequences have a seemingly random pairwise sequence similarity. The novelty of this work is in the particular combination of tools and sampling techniques that ascertained good performance comparable or better to existing state-of-the-art sequence comparison methods. Additionally, since this method does not need to generate alignments it is also orders of magnitudes faster. The code is available at https://github.com/Rostlab/EAT.
| Type: | Article |
|---|---|
| Title: | Contrastive learning on protein embeddings enlightens midnight zone |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/nargab/lqac043 |
| Publisher version: | https://doi.org/10.1093/nargab/lqac043 |
| Language: | English |
| Additional information: | © The Author(s) 2022. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10150829 |
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