CRS4 Biosciences research and development is focused on finding ways to make effective use of the big amount of data that flows from biomedical labs and high-throughput experiments.
We work with connecting data to knowledge, improving NGS technology, integrating and standardizing vast amounts of data coming from heterogeneous sources, developing new data analysis approaches and building enabling technologies to bring all of this to biomedical and life science researchers.
NON INVASIVE ANALYSIS OF SOMATIC MUTATIONS IN CANCER
The project aims to develop a non-invasive protocol to analyze the genetic profile of ctDNA (circulating tumor DNA) extracted from liquid biopsy of haematological and oncological patients, through the application of next generation sequencing technologies (NGS) on a panel of genes.
NIASMIC, promoted by the regional agency Sardegna Ricerche through the "Cluster top-down actions" program, is financed through the POR FESR of the Autonomous Region of Sardinia 2014-2020
CRS4 groups: Data Engineering & Computing, Biosciences, Next Generation Sequencing Core
CRS4 Role: Coordinator
Partner: AOB, Yenetics, NUREX, KITOS, BGT-Italia, Chrono-Benessere, Microtec, ARDEA.
Website: http://niasmic.crs4.it/
Funder: POR FESR SARDEGNA 2014 – 2020 ASSE PRIORITARIO 1 “RICERCA SCIENTIFICA, SVILUPPO TECNOLOGICO E INNOVAZIONE” AZIONE 1.1.4
Reference: Programma Azioni cluster top-down
Period: 2018 - 2020
Status: Execution
Contract type: Sovvenzione RSI/RDI Grant
People involved:
GENETIC MODIFIERS PREDISPOSING TO CKD IN ALPORT
Alport Syndrome (AS) and thin basement membrane nephropathy (TBMN) are inherited glomerulopathies presenting with familial microscopic hematuria (MH) since childhood.
AS follows X-linked (COL4A5) or autosomal recessive inheritance (COL4A3/COL4A4) and patients usually progress to end-stage renal disease (ESRD) by the fourth decade of life.
About 40-50% of TBMN cases are caused by heterozygous COL4A3/A4 mutations and most patients follow mild course with isolated MH; however recently we and others published work showing that a subset of patients develop focal segmental glomerulosclerosis and progressive kindly function decline while 15-30% of TBMN patients progress to ESRD, usually after the sixth decade. The clinical presentation can be complex and he full phenotypic spectrum behaves as a multifactorial condition, implicating primary genes, modifier genes and environmental factors.
A key unanswered question is why some patients follow a mild course with isolated MH or low grade proteinuria, but others with the same primary mutations develop progressive renal dysfunction.
Using a candidate gene approach, we and others described evidence of modifier genes, but much remains unexplained. To address this we will use unbiased Whole-Exome-Sequencing in a large population of patients harbouring a limited number of pathogenic heterozygous COL4A mutations. The size and relative homogeneity of our cohort, both in terms of the shared Cypriot genetic background and the small number of COL4A mutations, will maximize power to identify common and rare variants associated with disease progression and we will seek replication of findings in patients from other European populations. Candidate genetic modifiers will be recapitulated on Alport mice models in order to provide proof-of-principle for their contributory effect.
We anticipate that such functional modifiers may play a similar role in the general population as factors predisposing to renal impairment by aging. This, in turn may pave the way for new therapeutic approaches.
CRS4 groups: Data Engineering & Computing, Biosciences, Next Generation Sequencing Core
CRS4 Role: Partner
Funder: European Renal Association – European Dialysis and Transplant Association
Period: 2016 - 2019
Status: Execution
Contract type: Sovvenzione RSI/RDI Grant
People involved:
