Infraestructura de Medicina de Precisión asociada a la Ciencia y la Tecnología
Advances in genomic medicine have significantly improved the understanding of diseases and have proven to be a key element in the implementation of precision medicine in healthcare to improve diagnosis, prognosis, and treatment. The IMPaCT-Genomics initiative has developed a basic platform and workflows to evaluate undiagnosed cases with suspected genetic disease, including complex hereditary cancer cases, which have not been solved by standard healthcare tools.
However, today one of the greatest challenges associated with sequencing technologies is the interpretation of variants of unknown meaning (VSD) that have no clinical applicability. In patients with suspected hereditary cancer, it is common to identify multiple VSDs in the genomes and exomes analyzed, which justifies the need for additional studies to determine a definitive classification of the variant and achieve the genetic diagnosis that the family needs. In addition, functional genomics together with artificial intelligence promise to simplify and speed up genetic interpretation thanks to the integration of predictive methods with the growing knowledge of genetic predisposition to cancer.
The main objective of IMPaCT_VUSCan is to implement a comprehensive functional genomics platform within the IMPaCT Genomics infrastructure, to promote the resolution of a greater number of diagnoses of families with suspected familial cancer. In this way, the information generated by the different massive sequencing omics (WGS, WES, RNASeq, etc.) together with the development of new in silico analyses will allow the selection of candidate VSDs and, through functional validations, to offer a better interpretation of these, promoting the final diagnostic determination of the patient. Likewise, the results obtained will be integrated through tools based on artificial intelligence to offer a tool to support better clinical decision-making that could be implemented within the National Health System (SNS).
With the ultimate objective of improving the diagnosis of cases with suspected hereditary cancer that has not been resolved by the usual NHS tools, the following sub-objectives IMPaCT_VUSCan defined:
The following interdisciplinary proposal will contribute to the advancement of new biomedical applications that directly benefit society. Thus, it will allow the development of bioinformatics tools, workflows at the national level for the functional validation of variants of unknown meaning that guide clinical decision-making and will allow expanding knowledge about genes with susceptibility to familial cancer that will be reflected in new clinical recommendation guidelines. The data will also be accessible in public databases, contributing to initiatives such as 1+MG/B1MG or EU Mission Cancer.
On the other hand, this approach will improve the diagnostic performance of hereditary cancer cases. This will help establish the patient’s prognosis and take the best therapeutic approach for the patient. In addition, it will allow better monitoring and advice to their relatives in case they are carriers and relieve the stress associated with those who do not. Overall, the work strategies established in IMPaCT_VUSCan will allow for better management of cases with hereditary cancer in society and promote social awareness about familial cancer.