The rapid expansion of genetic sequencing since Sanger’s contribution has helped to boost the ranking of papers describing ways to analyse the sequences. A prime example is BLAST (Basic Local Alignment Search Tool), which for two decades has been a household name for biologists wanting to work out what genes and proteins do. Users simply have to open the program in a web browser and plug in a DNA, RNA or protein sequence. Within seconds, they will be shown related sequences from thousands of organisms — along with information about the function of those sequences and even links to relevant literature. So popular is BLAST that versions8, 9 of the program feature twice on the list, at spots 12 and 14.
But owing to the vagaries of citation habits, BLAST has been bumped down the list by Clustal, a complementary programme for aligning multiple sequences at once. Clustal allows researchers to describe the evolutionary relationships between sequences from different organisms, to find matches among seemingly unrelated sequences and to predict how a change at a specific point in a gene or protein might affect its function. A 1994 paper10 describing ClustalW, a user-friendly version of the software, is currently number 10 on the list. A 1997 paper11 on a later version called ClustalX is number 28.
The team that developed ClustalW, at the European Molecular Biology Laboratory in Heidelberg, Germany, had created the program to work on a personal computer, rather than a mainframe. But the software was transformed when Julie Thompson, a computer scientist from the private sector, joined the lab in 1991. “It was a program written by biologists; I’m trying to find a nice way to say that,” says Thompson, who is now at the Institute of Genetics and Molecular and Cellular Biology in Strasbourg, France. Thompson rewrote the program to ready it for the volume and complexity of the genome data being generated at the time, while also making it easier to use.
The teams behind BLAST and Clustal are competitive about the ranking of their papers. It is a friendly sort of competition, however, says Des Higgins, a biologist at University College Dublin, and a member of the Clustal team. “BLAST was a game-changer, and they’ve earned every citation that they get.”