Personalised medicine is once again in the spotlight with the completion of a new computational model for cancer genes developed by researchers at the Barcelona Supercomputer center.
The new method, called SMUFIN (Somatic Mutations Finder) is specifically designed to increase the speed at which cancer genomes, and their associated mutations, can be analysed. Furthermore SMUFIN can accurately identify practically all types of genetic changes involved in the onset and progression of cancer, including large-scale chromosome rearrangements which, until now, have been hard to detect.
This new computational method has applications in personalised medicine, allowing doctors not only to gain insights into the mutations of cancer so that patients can be treated promptly, but also providing information on the whole genome of the tumour including complex mutations that may have occurred.
In addition to personalised medicine, SMUFIN represents a new way of analysing genomes, which could also be applied to the study of the genetics underlying many other illnesses.
The research was published online in the journal of Nature Biotechnology at the end of October. The article describes the characteristics of SMUFIN, which has been developed by the computational genomics group at Barcelona Supercomputing Center (BSC).
The team is led by David Torrents, Research Professor ICREA (Catalan Institution for Research and Advanced Studies) at the BSC, in collaboration with research groups at Barcelona’s Hospital Clínic and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), the University Institute of Oncology of Asturias at the University of Oviedo (IUOPA), the European Molecular Biology Laboratory (EMBL, Heidelberg) and the Spanish National Genome Analysis Center (CNAG, Barcelona).
The article published in Nature Biotechnology explains how SMUFIN, in addition to making the analysis faster and more cost-effective, is able to reveal hard-to-detect genetic alterations in aggressive tumours. Using SMUFIN to analyse two types of aggressive cancer samples, a blood tumor (mantle cell lymphoma) and one of the nervous system (pediatric medulloblastoma), has allowed the discovery of almost all the types of mutations occurring in their genomes for the first time and with over 90 per cent accuracy.
This includes alterations in the organisation of chromosomes, which have not been revealed by methods used to date. This represents the first step necessary to understanding how these chromosome alterations affect the evolution and aggressiveness of the tumour.
One of key innovations while developing SMUFIN is that the new method represents a radical change in the method in the way genomes are analysed. Up until now identifying mutations responsible for the appearance of tumours has involved comparing genomes taken from the tumour with genomes obtained from healthy cells from the same patient via a reference human genome.
This lengthy and complex process results in the loss of a considerable amount of information and makes it difficult to identify many mutations which have an impact on the tumour. This analysis is also executed on different computer programs in succession, each one of which is only capable of detecting certain types of variations.
One of the defining characteristics of SMUFIN is that all the analysis is undertaken within the single programme, which is what makes the analysis more efficient than traditional methods.
SMUFIN undertakes a direct comparison between the genome of healthy cells and cells from the tumour in the same patient and determines the location of almost all types of mutations at once, without requiring the use of several programs. This results in a quicker, more complete and cost-effective analysis.
SMUFIN makes it possible for a large number of research groups to study their patients’ genomes in a way previously unavailable to them. In addition, when used by supercomputing centres, SMUFIN allows mutations to be identified in hundreds or thousands of cancer genomes in just a few days. In this regard, BSC is already participating in the largest global cancer genome initiative through the International Cancer Genome Consortium (ICGC), which aims to analyse the genomes of thousands of patients in order to study the genetic bases of the onset and evolution of a large number of tumour types.
Development work on SMUFIN began at Barcelona Supercomputing Center in 2011 by the genomics team, which is part of the BSC-CRG-IRB (Barcelona Supercomputing Center, Genomic Regulation Center and Institute for Research in Biomedicine Barcelona) Joint Programme in Computational Biology.
SMUFIN was developed in two research environments in which the BSC participates. One is the Chronic Lymphocytic Leukemia Genome Project, which aims to research leukemia by analysing the genome of more than 500 patients.
The development also forms part of the National Severo Ochoa Programme, with which Barcelona Supercomputing Center is driving forward the creation of bioinformatics tools capable of managing and analysing big amounts of biomedical data which are necessary to make personalised medicine possible, among other tools.