Publication Analysis 2009-2015
by Kathleen Gransalke, Labtimes 06/2017
Modern protein research heavily depends on high-tech equipment and computer power. Research hot spots are in Martinsried, Heidelberg and Hinxton.
Proteins are the workhorses in the cell – they transport cargo, they provide structural support, they communicate important information. Although it’s clear that humans possess about 25,000 genes, of which 20,000 are protein-coding, researchers disagree about the total number of proteins or the number of different polypeptides per cell. Thanks to alternative splicing and post-translation modifications, for instance, some researchers predict that a human cell could hold as much as 80,000 different polypeptides and two billion proteins in total.
Sticking with superlatives, the current publication analysis intends to expose the most-cited protein researchers in Europe. But first, we’ll take a more general look at the best-performing nations in this discipline. As we did earlier, for this part of the analysis, we had to restrict our sources to those journals that specifically publish protein research. Protein papers, however, often end up in biochemistry or molecular biology journals, which have a rather wide scope, including genetic studies, for instance. For this reason, we decided to exclude some prominent journals in the field, the likes of EMBO Journal or The FASEB Journal. This may explain the low number of publications in our nations’ performance table. This restriction, however, was abrogated for the most-cited authors ranking.
Germany takes the lead position with more than 80,000 total citations, far ahead of England with about 50,000 citations. With regard to the citation-per-article ratio, one nation is as good as the other (18.3 vs 18.6). Astonishingly, Spain in third position is only slightly behind England, regarding total citations, and ahead of both Germany and England, when it comes to average citations per paper. As expected, Eastern Europe, a stronghold of analytical sciences, performs well in protein research, with Poland in 12th place, the Czech Republic in 14th place and Russia occupying the 16th spot. Leaders in the citations-per-article category are Denmark (22.0), Switzerland (21.6) and The Netherlands (20.4). Compared with their US colleagues, European protein researchers again wrote more papers, gathering more citations, but on average, articles, reviews and proceedings papers from the USA received more attention aka citations.
Let’s move on to the top papers in the field. Four of the five most-cited publications revolve around bioinformatics tools and databases. Thus, the paper in second place introduces the Clustal Omega programme, developed by scientists at the Conway Institute in Dublin, which allows the alignment between three or more protein sequences (www.ebi.ac.uk/Tools/msa/clustalo). Publications in third and fourth place describe the Pfam protein families’ database (http://pfam.xfam.org). Founded in 1995 by Erik Sonnhammer, Sean Eddy and Richard Durbin, the latest version of the database, version 31.0, contains a total of 16,712 families and 604 clans. The fifth most-cited publication in protein research is all about the Search Tool for the Retrieval of Interacting Genes/Proteins, STRING (https://string-db.org). This database comprises all known and predicted protein-protein interactions, be it direct (physical) or indirect (functional) associations. Version 10.0 contains information on more than nine million proteins from about 2,000 organisms.
Only the most-cited paper in protein research, with well over 3,000 citations, is not about computational tools and databases. Amongst others Matthias Mann, Chuna Ram Choudhary and Jesper Olsen analysed, by high resolution mass spectrometry, lysine acetylation of proteins. These post-translational modifications steer many cellular processes, such as chromatin remodelling and splicing. The team identified 3,600 lysine acetylation sites on 1,750 proteins.
All three authors, Mann (1st), Choudhary (21st) and Olsen (6th), made our top 30 – thanks in large to this article. Here, we should mention a few limitations of this ranking. First, we only included researchers, who are interested in more general aspects of proteins or protein families. Second, publication of those researchers, who combine their protein studies with, for instance, work on genes or epigenetics (see Peer Bork, 2nd, or Christian von Mering, 7th) must contain a significant amount of the keywords “protein”, “peptide” or “proteomics”. By the way, when compiling our top 30 list, we were reminded of the benefits of having a ResearcherID. In more than one case, we would have missed a few papers (and citations) because the researcher’s name was misspelled in the Web of Science database.
Without further ado, let’s look at the most-cited protein researchers in Europe in more detail. Remarkable is a clear geographic clustering: The Max Planck Institute (MPI) for Biochemistry in Martinsried, Germany, and the European Molecular Biology Labs in Heidelberg, Germany, and Hinxton, UK, are premium research hubs for protein research. Not less than five scientists among our top 30 are affiliated with the MPI for Biochemistry. One of them is our ranking’s number one, Matthias Mann, expert in mass spectrometry proteomics. He identified and quantified the first model proteome (yeast) and, according to his Institute, is the first German researcher with an h-index higher than 200.
Jürgen Cox (8th), who’s also at the MPI in Martinsried, develops computational methods that enable the identification and quantification of proteins. Trained as a theoretical physicist, Cox has made a name for himself as the creator of the MaxQuant programme, a “quantitative proteomics software package designed for analysing large-scale mass-spectrometric data sets”. Also at the same institute, chemist and editor-in-chief of the Proteomes journal, Jacek Wisniewski (25th), is perhaps best known for developing a method that allows proteins in fixed tissue samples to be used for mass spectrometry. “In the beginning, we weren’t taken seriously at all – hardly anyone believed that tissue samples that had been soaked in formalin could still yield any usable information about the proteins,” Wisniewski once said. Tipped for a Nobel Prize for years, Franz-Ulrich Hartl (28th) studies, at the structural and functional level, how assistant proteins called chaperones help other proteins to fold correctly. During his acceptance speech for the 2011 Lasker Award, Hartl reminded us that “our true reward as scientists is the privilege of doing something that we enjoy so deeply and that doesn’t feel like work at all”.
As mentioned above, the European Molecular Biology Laboratories in Heidelberg and Hinxton are home to a large number of highly-cited protein researchers. In Heidelberg, Peer Bork (2nd) focusses not only on proteins and their interactions but also on genes and the gut microbiome. Ivica Letunic (19th) used to work in Bork’s lab but is now boss of biocyte solutions, a company developing “customised, fast and high quality bioinformatics solutions”. Tobias Doerks (22nd), who sadly passed away earlier this year, worked on the functional predictions of proteins, while Toby Gibson (23rd) studies protein sequences and interactions with computational power. His lab also hosts the Eukaryotic Linear Motif (ELM) resource, “dedicated to short functional site motifs in modular protein sequences”.
At the Hinxton site, Alex Bateman (4th) is interested in protein and RNA sequences, and leads the protein sequence resources cluster (UniProt, Pfam, MEROPS). Rolf Apweiler (13th) develops standards for proteomics data; his team curates the PRIDE (PRoteomics IDEntifications) and the IntAct (Molecular Interaction) databases. Henning Hermjakob (20th), meanwhile, develops tools and resources for the “representation, deposition, distribution and analysis of pathway and systems biology data”.
Our top 30 also includes two female researchers, Carol Robinson (11th) and Ruth Nussinov (12th). Robinson was the first female professor of Chemistry at both the University of Cambridge and subsequently, the University of Oxford. She also uses mass spectrometry to elucidate the 3D structure of proteins and, more recently, study the interaction of proteins with co-factors, nucleic acids and other proteins.
As in many other disciplines, being a successful researcher not only depends on hard work but also on serendipity in large quantities. “Breakthroughs happen by accident. They are unexpected and you capitalise on them. They are impossible to spot,” Carol Robinson said in an interview. Franz-Ulrich Hartl agrees, “I am well aware that our discoveries were only possible because many others who came before us laid the foundation. This, and a large quantity of good fortune, allowed us to make the surprising finding, in the late 1980s.”
With more lucky circumstances and technological developments, perhaps the question of the total number of proteins in a human cell could soon be solved.
View the Picture: Most Cited Authors
Last Changed: 28.11.2017