Biology subjects

Conticello, S. G.

Publications and source records attributed to Conticello, S. G..

5 recordsLinked to original sources

bioRxiv2021

Detecting cell-of-origin and cancer-specific features of cell-free DNA with Nanopore sequencing

The Oxford Nanopore (ONT) platform provides portable and rapid genome sequencing, and its ability to natively profile DNA methylation without complex sample processing is attractive for clinical sequencing. We recently demonstrated ONT shallow whole-genome sequencing to detect copy number alterations (CNA) from the circulating tumor DNA (ctDNA) of cancer patients. Here, we show that cell-type and cancer-specific methylation changes can also be detected, as well as cancer-associated fragmentation signatures. This feasibility study suggests that ONT shallow WGS could be a powerful tool for liquid biopsy, especially real-time medical applications.

genomics↗

bioRxiv2020

Nanopore sequencing from liquid biopsy: analysis of copy number variations from cell-free DNA of lung cancer patients

Alterations in the genetic content, such as Copy Number Variations (CNVs) is one of the hallmarks of cancer and their detection is used to recognize tumoral DNA. Analysis of cell-free DNA from plasma is a powerful tool for non-invasive disease monitoring in cancer patients. Here we exploit third generation sequencing (Nanopore) to obtain a CNVs profile of tumoral DNA from plasma, where cancer-related chromosomal alterations are readily identifiable. Compared to Illumina sequencing -the only available alternative- Nanopore sequencing represents a viable approach to characterize the molecular phenotype, both for its ease of use, costs and rapid turnaround (6 hours).

cancer biology↗

bioRxiv2020

Evidence for RNA editing in the transcriptome of 2019 Novel Coronavirus

The COVID-19 outbreak has become a global health risk and understanding the response of the host to the SARS-CoV-2 virus will help to contrast the disease. Editing by host deaminases is an innate restriction process to counter viruses, and it is not yet known whether it operates against Coronaviruses. Here we analyze RNA sequences from bronchoalveolar lavage fluids derived from infected patients. We identify nucleotide changes that may be signatures of RNA editing: Adenosine-to-Inosine changes from ADAR deaminases and Cytosine-to-Uracil changes from APOBEC ones. A mutational analysis of genomes from different strains of human-hosted Coronaviridae reveals mutational patterns compatible to those observed in the transcriptomic data. Our results thus suggest that both APOBECs and ADARs are involved in Coronavirus genome editing, a process that may shape the fate of both virus and patient. For the casual ReaderJust to make a few things clear: - RNA editing and DNA editing are PHYSIOLOGICAL processes. Organisms uses them to (a) try to fight viruses, (b) increase heterogeneity inside cells (on many levels), (c) recognise their own RNA. - our work suggests that: (a) cells use RNA editing in trying to deal with Coronaviruses. We don't know to what extent they succeed (and it would be nice if we could help them). (b) Whatever happens, mutations inserted by RNA editing fuel viral evolution. We don't know whether viruses actively exploit this. - If you (scientist or not) think our work suggests ANYTHING ELSE, contact us. It can be a first step to help fight these !@#$ coronavirus, or towards a Nobel prize - but we need to discuss it thoroughly. - If you think these cellular processes are fascinating, join the club and contact us. We can have a nice cup of tea while chatting how wondrous nature is at coming up with extraordinary solutions...

bioinformatics↗

bioRxiv2018

Dimerisation of APOBEC1 is dispensable for its RNA editing activity

The AID/APOBECs are DNA/RNA deaminases whose mutagenic activity has been linked to cancer. Among them, APOBEC1 physiologically partakes into a complex that edits a CAA codon into UAA Stop codon in the transcript of Apolipoprotein B (APOB), a protein crucial in the transport of lipids in the blood. Catalytically inactive mutants of APOBEC1 have a dominant negative effect on its activity, as they compete for the targeting of the APOB mRNA. Here we titrate APOBEC1-mediated editing in presence of catalytically inactive chimeras and mutants of APOBEC1, and we show that APOBEC1 inability to dimerise is the main determinant for its activity. This property is especially evident in an APOBEC1 mutant (L173A G227A) with increased activity on RNA despite decreased self-interaction. Moreover, dimerisation protects APOBEC1 from degradation and regulates its availability. Considering APOBEC1 capability to target DNA, we demonstrate that increased availability of the protein due to dimerisation leads to increase in the DNA damage induced by APOBEC1. These findings demonstrate that dimerisation, a property common to other APOBECs targeting DNA, might represent another layer in the regulation of this editing enzyme. BULLET POINTSO_LIAPOBEC1 inability to dimerise is the main determinant for its activity. C_LIO_LIDimerisation protects APOBEC1 from degradation and regulates its availability. C_LIO_LIAlterations in the balance between monomeric and dimeric APOBEC1 increase DNA damage. C_LI

molecular biology↗

bioRxiv2018

Mutational likeliness and entropy help to identify driver mutations and their functional role in cancer

Alterations in cancer genomes originate from mutational processes taking place throughout oncogenesis and cancer progression. We show that likeliness and entropy are two properties of somatic mutations crucial in cancer evolution, as cancer-driver mutations stand out, with respect to both of these properties, as being distinct from the bulk of passenger mutations. Our analysis can identify novel cancer driver genes and differentiate between gain and loss of function mutations.

cancer biology↗