UniRule: a unified rule resource for automatic annotation in the UniProt Knowledgebase
Authors: MacDougall Alistair , Volynkin Vladimir , Saidi Rabie , Poggioli Diego , Zellner Hermann , Hatton-Ellis Emma , Joshi Vishal , O’Donovan Claire , Orchard Sandra , Auchincloss Andrea H , Baratin Delphine , Bolleman Jerven , Coudert Elisabeth , de Castro Edouard , Hulo Chantal , Masson Patrick , Pedruzzi Ivo , Rivoire Catherine , Arighi Cecilia , Wang Qinghua , Chen Chuming , Huang Hongzhan , Garavelli John , Vinayaka C R , Yeh Lai-Su , Natale Darren A , Laiho Kati , Martin Maria-Jesus , Renaux Alexandre , Pichler Klemens ,   The UniProt Consortium, Bateman Alex , Bridge Alan , Wu Cathy , Arighi Cecilia , Breuza Lionel , Coudert Elisabeth , Huang Hongzhan , Lieberherr Damien , Magrane Michele , Martin Maria J , McGarvey Peter , Natale Darren , Orchard Sandra , Pedruzzi Ivo , Poux Sylvain , Pruess Manuela , Raj Shriya , Redaschi Nicole , Aimo Lucila , Argoud-Puy Ghislaine , Auchincloss Andrea , Axelsen Kristian , Boutet Emmanuel , Bowler Emily , Britto Ramona , Bye-A-Jee Hema , Casals-Casas Cristina , Denny Paul , Estreicher Anne , Famiglietti Maria Livia , Feuermann Marc , Garavelli John S , Garmiri Penelope , Gos Arnaud , Gruaz Nadine , Hatton-Ellis Emma , Hulo Chantal , Hyka-Nouspikel Nevila , Jungo Florence , Laiho Kati , Le Mercier Philippe , Lock Antonia , Lussi Yvonne , MacDougall Alistair , Masson Patrick , Morgat Anne , Pilbout Sandrine , Pourcel Lucille , Rivoire Catherine , Ross Karen , Sigrist Christian , Speretta Elena , Sundaram Shyamala , Tyagi Nidhi , Vinayaka C R , Wang Qinghua , Warner Kate , Yeh Lai-Su , Zaru Rossana , Ahmed Shadab , Alpi Emanuele , Arminski Leslie , Bansal Parit , Baratin Delphine , Neto Teresa Batista , Bolleman Jerven , Chen Chuming , Chen Yongxing , Cuche Beatrice , Cukura Austra , De Castro Edouard , Ebenezer ThankGod , Gasteiger Elisabeth , Gehant Sebastien , Gonzales Leonardo , Hussein Abdulrahman , Ignatchenko Alexandr , Insana Giuseppe , Ishtiaq Rizwan , Joshi Vishal , Jyothi Dushyanth , Kerhornou Arnaud , Lombardot Thierry , Luciani Aurelian , Luo Jie , Mahmoudy Mahdi , Mishra Alok , Moulang Katie , Nightingale Andrew , Onwubiko Joseph , Pozzato Monica , Pundir Sangya , Qi Guoying , Rice Daniel , Saidi Rabie , Turner Edward , Vasudev Preethi , Wang Yuqi , Watkins Xavier , Zellner Hermann , Zhang Jian 
Published: May 2020

Abstract

Motivation
The number of protein records in the UniProt Knowledgebase (UniProtKB: https://www.uniprot.org) continues to grow rapidly as a result of genome sequencing and the prediction of protein-coding genes. Providing functional annotation for these proteins presents a significant and continuing challenge.

Results
In response to this challenge, UniProt has developed a method of annotation, known as UniRule, based on expertly curated rules, which integrates related systems (RuleBase, HAMAP, PIRSR, PIRNR) developed by the members of the UniProt consortium. UniRule uses protein family signatures from InterPro, combined with taxonomic and other constraints, to select sets of reviewed proteins which have common functional properties supported by experimental evidence. This annotation is propagated to unreviewed records in UniProtKB that meet the same selection criteria, most of which do not have (and are never likely to have) experimentally verified functional annotation. Release 2020_01 of UniProtKB contains 6496 UniRule rules which provide annotation for 53 million proteins, accounting for 30% of the 178 million records in UniProtKB. UniRule provides scalable enrichment of annotation in UniProtKB.

Availability and implementation
UniRule rules are integrated into UniProtKB and can be viewed at https://www.uniprot.org/unirule/. UniRule rules and the code required to run the rules, are publicly available for researchers who wish to annotate their own sequences. The implementation used to run the rules is known as UniFIRE and is available at https://gitlab.ebi.ac.uk/uniprot-public/unifire.