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Background Tumors are composed by a number of cancer cell subpopulations (subclones), characterized by a distinguishable set of mutations. This phenomenon, known as intra-tumor heterogeneity (ITH), may be studied using Copy Number Aberrations (CNAs). Nowadays ITH can be assessed at the highest possible resolution using single-cell DNA (scDNA) sequencing technology. Additionally, single-cell CNA (scCNA) profiles from multiple samples of the same tumor can in principle be exploited to study the spatial distribution of subclones within a tumor mass. However, since the technology required to generate large scDNA sequencing datasets is relatively recent, dedicated analytical approaches are still lacking. Results We present PhyliCS, the first tool which exploits scCNA data from multiple samples from the same tumor to estimate whether the different clones of a tumor are well mixed or spatially separated. Starting from the CNA data produced with third party instruments, it computes a score, the Spatial Heterogeneity score, aimed at distinguishing spatially intermixed cell populations from spatially segregated ones. Additionally, it provides functionalities to facilitate scDNA analysis, such as feature selection and dimensionality reduction methods, visualization tools and a flexible clustering module. Conclusions PhyliCS represents a valuable instrument to explore the extent of spatial heterogeneity in multi-regional tumour sampling, exploiting the potential of scCNA data.

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BackgroundIt is estimated that oncogenic gene fusions cause about 20% of human cancer morbidity. Identifying potentially oncogenic gene fusions may improve affected patients’ diagnosis and treatment. Previous approaches to this issue included exploiting specific gene-related information, such as gene function and regulation. Here we propose a model that profits from the previous findings and includes the microRNAs in the oncogenic assessment. We present a classifier called ChimerDriver for the classification of gene fusions as oncogenic or not oncogenic. ChimerDriver is based on a specifically designed neural network and trained on genetic and post-transcriptional information to obtain a reliable classification.Results and discussionThe designed neural network integrates information related to transcription factors, gene ontologies, microRNAs and other detailed information related to the functions of the genes involved in the fusion and the gene fusion structure. As a result, the performances on the test set reached 0.83 f1-score and 96% recall. The comparison with state-of-the-art tools returned comparable or higher results. Moreover, ChimerDriver performed well in a real-world case where 21 out of 24 validated gene fusion samples were detected by the gene fusion detection tool Starfusion.ConclusionsChimerDriver integrated transcriptional and post-transcriptional information in an ad-hoc designed neural network to effectively discriminate oncogenic gene fusions from passenger ones.

Making raw data available to the research community is one of the pillars of Findability, Accessibility, Interoperability, and Reuse (FAIR) research. However, the submission of raw data to public databases still involves many manually operated procedures that are intrinsically time-consuming and error-prone, which raises potential reliability issues for both the data themselves and the ensuing metadata. For example, submitting sequencing data to the European Genome-phenome Archive (EGA) is estimated to take 1 month overall, and mainly relies on a web interface for metadata management that requires manual completion of forms and the upload of several comma separated values (CSV) files, which are not structured from a formal point of view. To tackle these limitations, here we present EGAsubmitter, a Snakemake-based pipeline that guides the user across all the submission steps, ranging from files encryption and upload, to metadata submission. EGASubmitter is expected to streamline the automated submission of sequencing data to EGA, minimizing user errors and ensuring higher end product fidelity.