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Fanfani, V.

Publications and source records attributed to Fanfani, V..

2 recordsLinked to original sources

A unified framework for geneset network analysis

Gene and protein interaction experiments provide unique opportunities to study their wiring in a cell. Integrating this information with high-throughput functional genomics data can help identifying networks associated with complex diseases and phenotypes.\n\nHere we propose a unified statistical framework to test network properties of single and multiple genesets. We focused on testing whether a geneset exhibits network properties and if two genesets are strongly interacting with each other.\n\nWe then assessed power and false discovery rate of the proposed tests, showing that tests based on a probabilistic model of gene and protein interaction are the most robust.\n\nWe implemented our tests in an open-source framework, called Python Geneset Network Analysis (PyGNA), which provides an integrated environment for network studies. While most available tools are designed as web applications, we designed PyGNA to be easily integrated into existing high-performance data analysis pipelines.\n\nOur software is available on GitHub (http://github.com/stracquadaniolab/pygna) and can be easily installed from PyPi or anaconda.

bioinformatics

Gene-level heritability analysis explains the polygenic architecture of cancer

Genome-wide association studies (GWAS) have found hundreds of single nucleotide polymorphisms (SNPs) associated with increased risk of cancer. However, the amount of heritable risk explained by these variants is limited, thus leaving most of cancer heritability unexplained. Recent studies have shown that genomic regions associated with specific biological functions explain a large proportion of the heritability of many traits. Since cancer is mostly triggered by aberrant genes function, we hypothesised that SNPs located in protein-coding genes could explain a significant proportion of cancer heritability. To perform this analysis, we developed a new method, called Bayesian Gene HERitability Analysis (BAGHERA), to estimate the heritability explained by all the genotyped SNPs and by those located in protein coding genes directly from GWAS summary statistics. By applying BAGHERA to the 38 cancers reported in the UK Biobank, we identified 1, 146 genes explaining a significant amount of cancer heritability. We found these genes to be tumour suppressors directly involved in the hallmark processes controlling the transformation from normal to cancer cell; moreover, these genes also harbour somatic driver mutation for many tumours, suggesting a two-hit model underpinning tumorigenesis. Our study provides new evidence for a functional role of SNPs in cancer and identifies new targets for risk assessment and patients stratification.

genetics