Nicola Crosetto

My main research interest is in developing and applying sequencing- and microscopy-based methods to investigate the interplay between genome structure, function, and fragility in health and disease, with a strong focus on cancer. In this arena, I am strongly committed to developing user-friendly and cost-effective methods that can be translated into useful clinical applications.

Over the years, I have developed numerous tools, including the first method for genome-wide mapping of DNA double-strand breaks (BLESS, Nat Meth 2013) and its downstream improvements (BLISS, Nat Commun 2017; sBLISS, Nat Prot 2020), as well as a variety of sequencing- (CUTseq, Nat Commun 2019; GPSeq, Nat Biotechnol 2020; COVseq, Nat Commun 20221) and microscopy-based methods (HD-FISH, Nat Meth 2013; FuseFISH, Cell Rep 2014; RollFISH, Comm Bio 2018; iFISH, Nat Commun 2019; FRET-FISH, Nat Commun 2022) for studying various aspects of genome structure and fragility.

Publications

  • 06/2021 - Nature Communications

    COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance

    While mass-scale vaccination campaigns are ongoing worldwide, genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the emergence and global spread of viral variants of concern (VOC). Here, we present a streamlined workflow-COVseq-which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms from hundreds of SARS-CoV-2 […]

  • 10/2020 - Nature Biotechnology

    GPSeq reveals the radial organization of chromatin in the cell nucleus

    With the exception of lamina-associated domains, the radial organization of chromatin in mammalian cells remains largely unexplored. Here we describe genomic loci positioning by sequencing (GPSeq), a genome-wide method for inferring distances to the nuclear lamina all along the nuclear radius. GPSeq relies on gradual restriction digestion of chromatin from the nuclear lamina toward the […]

  • 10/2019 - Nature Communications

    CUTseq is a versatile method for preparing multiplexed DNA sequencing libraries from low-input samples

    Current multiplexing strategies for massively parallel sequencing of genomic DNA mainly rely on library indexing in the final steps of library preparation. This procedure is costly and time-consuming, because a library must be generated separately for each sample. Furthermore, library preparation is challenging in the case of fixed samples, such as DNA extracted from formalin-fixed […]

  • 04/2019 - Nature Communications

    iFISH is a publically available resource enabling versatile DNA FISH to study genome architecture

    DNA fluorescence in situ hybridization (DNA FISH) is a powerful method to study chromosomal organization in single cells. At present, there is a lack of free resources of DNA FISH probes and probe design tools which can be readily applied. Here, we describe iFISH, an open-source repository currently comprising 380 DNA FISH probes targeting multiple […]

  • 05/2017 - Nature Communications

    BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks

    Precisely measuring the location and frequency of DNA double-strand breaks (DSBs) along the genome is instrumental to understanding genomic fragility, but current methods are limited in versatility, sensitivity or practicality. Here we present Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on […]