New computational method allows the identification of genetic alterations in cancer patients within hours

IDIBAPS and Hospital Clínic have participated in the development of a new computational method that enables to detect genetic changes responsible for the onset and progression of tumors in a simple, quick and precise way. The research is published in the latest issue of the prestigious journal Nature Biotechnology. This methodology, called SMUFIN (Somatic Mutations Finder), is capable of analyzing the complete genome of a tumor and identifying its mutations in a few hours. In addition, it is able to identify alterations which had previously not been revealed, even using methods which require the use of supercomputers over several weeks.

The work has been developed by the Computational Genomics Group at Barcelona Supercomputing Center, led by Dr. David Torrents, in co-operation with the team led by Dr. Elías Campo, head of the IDIBAPS group Human and experimental functional oncomorphology and Research Director at Hospital Clínic. 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 Centre (CNAG, Barcelona), have also collaborated.

A new way to analyze genomes

One of SMUFIN’s main innovations is that it represents a radical change in the method by which genomes are analyzed. To date, identifying mutations responsible for the appearance of tumors has involved comparing genomes taken from the tumor with genomes obtained from healthy cells from the same patient via a reference human genome, which is used as a guide. 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 tumor. This analysis is also executed on different computer programs in succession, each one of which is only capable of detecting certain types of variations.

SMUFIN, meanwhile, undertakes a direct comparison between the genome of healthy cells and cells from a tumor 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 much quicker and more complete analysis.

Advances in the research of aggressive tumors

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 tumors. Using SMUFIN to analyze 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% accuracy. This includes alterations in the organization 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 tumor.

Boost for biomedical research and advance towards personalized medicine

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 centers, 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 analyze the genomes of thousands of patients in order to study the genetic bases of the onset and evolution of a large number of tumor types.

This new method also represents a decisive step towards personalized medicine, where the genome analysis of each patient will enable faster and more accurate diagnosis. It will also allow the development and application of personalized treatments which are less invasive than those currently used.

A development within the framework of CLL and the Severo Ochoa programme

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 Centre and Institute for Research in Biomedicine Barcelona) Joint Programme in Computational Biology.

SMUFIN was developed in two research environments in which the center participates. One is the Chronic Lymphocytic Leukemia Genome Project, of which the scientific directors are Elías Campo (Hospital Clínic, IDIBAPS) and Carlos López Otín (University of Oviedo), and which aims to research leukemia by analyzing 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 analyzing big amounts of biomedical data which are necessary to make personalized medicine possible, among other tools.

Article reference:

Comprehensive characterization of complex structural variations in cancer by directly comparing genome sequence reads.

Moncunill V, Gonzalez S, Beà S, Andrieux LO, Salaverria I, Royo C, Martinez L, Puiggròs M, Segura-Wang M, Stütz AM, Navarro A, Royo R, Gelpí JL, Gut IG, López-Otín C, Orozco M, Korbel JO, Campo E, Puente XS, Torrents D.

Nat Biotechnol. 2014 Oct 26. doi: 10.1038/nbt.3027. [Epub ahead of print]