The Network of Cancer Genes (NCG) is a manually curated repository of 2372 genes whose somatic modifications have known or predicted cancer driver roles. These genes were collected from 275 publications, including two sources of known cancer genes and 273 cancer sequencing screens of more than 100 cancer types from 34,905 cancer donors and multiple primary sites. This represents a more than 1.5-fold content increase compared to the previous version. NCG also annotates properties of cancer genes, such as duplicability, evolutionary origin, RNA and protein expression, miRNA and protein interactions, and protein function and essentiality. NCG is accessible at http://ncg.kcl.ac.uk/.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1612-0) contains supplementary material, which is available to authorized users.
Background Genetic alterations of somatic cells can drive non-malignant clone formation and promote cancer initiation. However, the link between these processes remains unclear and hampers our understanding of tissue homeostasis and cancer development. Results Here, we collect a literature-based repertoire of 3355 well-known or predicted drivers of cancer and non-cancer somatic evolution in 122 cancer types and 12 non-cancer tissues. Mapping the alterations of these genes in 7953 pan-cancer samples reveals that, despite the large size, the known compendium of drivers is still incomplete and biased towards frequently occurring coding mutations. High overlap exists between drivers of cancer and non-cancer somatic evolution, although significant differences emerge in their recurrence. We confirm and expand the unique properties of drivers and identify a core of evolutionarily conserved and essential genes whose germline variation is strongly counter-selected. Somatic alteration in even one of these genes is sufficient to drive clonal expansion but not malignant transformation. Conclusions Our study offers a comprehensive overview of our current understanding of the genetic events initiating clone expansion and cancer revealing significant gaps and biases that still need to be addressed. The compendium of cancer and non-cancer somatic drivers, their literature support, and properties are accessible in the Network of Cancer Genes and Healthy Drivers resource at http://www.network-cancer-genes.org/.
The Network of Cancer Genes (NCG) is a manually curated repository of 2,372 genes whose somatic modifications have a known or predicted cancer driver role.These genes were collected from 275 publications, including two sources of known cancer genes and 273 cancer sequencing screens of 119 cancer types in 31 primary sites from 34,905 cancer donors. This represents a more than 1.5-fold increase in content as compared to the previous version. NCG also annotates properties of cancer genes, such as duplicability, evolutionary origin, RNA and protein expression, miRNA and protein interactions, protein function and essentiality. NCG is accessible at http://ncg.kcl.ac.uk/.
Since the small RNA-sequencing (sRNA-seq) technology became available, it allowed the discovery of thousands new microRNAs (miRNAs) in humans and many other species, providing new data on these small RNAs (sRNAs) of high biological and translational relevance. MiRNA discovery has not yet reached saturation, even in the most studied model organisms, and many researchers are using sRNA-seq in studies with different aims in biomedicine, fundamental research and in applied animal sciences. We review several miRNA discovery and characterization software tools that implement different strategies, providing a useful guide for researchers to select the programs best suiting their study objectives and data. After a brief introduction on miRNA biogenesis, function and characteristics, useful to understand the biological background considered by the algorithms, we survey the current state of miRNA discovery bioinformatics discussing 26 different sRNA-seq-based miRNA prediction software and toolkits released in the past 6 years, including 15 methods specific for miRNA prediction and 11 more general-purpose software suites for sRNA-seq data analysis. We highlight the main features of mature miRNAs and miRNA precursors considered by the methods categorizing them according to prediction strategy and implementation. In addition, we describe a typical miRNA prediction and analysis workflow by delineating the objectives, potentialities and main steps of sRNA-seq data analysis projects, from preparatory data processing to miRNA prediction, quantification and diverse downstream analyses. Finally, we outline the caveats affecting sRNA-seq-based prediction tools, and we indicate the possibilities offered by data set pooling and by integration with other types of high-throughput sequencing data.
Multiplexed imaging technologies enable the study of biological tissues at single-cell resolution while preserving spatial information. Currently, high-dimension imaging data analysis is technology-specific and requires multiple tools, restricting analytical scalability and result reproducibility. Here we present SIMPLI (Single-cell Identification from MultiPLexed Images), a flexible and technology-agnostic software that unifies all steps of multiplexed imaging data analysis. After raw image processing, SIMPLI performs a spatially resolved, single-cell analysis of the tissue slide as well as cell-independent quantifications of marker expression to investigate features undetectable at the cell level. SIMPLI is highly customisable and can run on desktop computers as well as high-performance computing environments, enabling workflow parallelisation for large datasets. SIMPLI produces multiple tabular and graphical outputs at each step of the analysis. Its containerised implementation and minimum configuration requirements make SIMPLI a portable and reproducible solution for multiplexed imaging data analysis. Software is available at “SIMPLI [https://github.com/ciccalab/SIMPLI]”.
Medulloblastoma with extensive nodularity (MBEN) are cerebellar tumors with two histologically distinct compartments and varying disease course. In some children MBEN progresses, while others show spontaneous differentiation into more benign tumors. However, the mechanisms that control the tug-of-war between proliferation and differentiation are not well understood. Here, we dissected this process with a multi-modal single cell transcriptome analysis. We found that the internodular MBEN compartment comprised proliferating early cerebellar granular neuronal precursors (CGNP)-like tumor cells as well as stromal, vascular, and immune cells. In contrast, the nodular compartment consisted of postmitotic, neuronally differentiated MBEN cells. Both compartments were connected through an intermediate cell stage of actively migrating CGNPs. Furthermore, astrocyte-like tumor cells were identified that had branched off the main CGNP developmental trajectory. Cells with an astroglial phenotype were found in close proximity to migrating, late CGNP-like and postmitotic neuronally differentiated cells. Our study reveals how the spatial tissue organization is linked to the developmental trajectory of proliferating tumor cells through a migrating precursor stage into differentiated tumor cells with a more benign phenotype. We anticipate that our framework for integrating single nucleus RNA-sequencing and spatial transcriptomics will help to uncover intercompartmental interactions also in other cancers with varying histology.
MicroRNA-offset RNAs (moRNAs) are microRNA-like small RNAs generated by microRNA precursors. To date, little is known about moRNAs and bioinformatics tools to inspect their expression are still missing. We developed miR&moRe2, the first bioinformatics method to consistently characterize microRNAs, moRNAs, and their isoforms from small RNA sequencing data. To illustrate miR&moRe2 discovery power, we applied it to several published datasets. MoRNAs identified by miR&moRe2 were in agreement with previous research findings. Moreover, we observed that moRNAs and new microRNAs predicted by miR&moRe2 were downregulated upon the silencing of the microRNA-biogenesis pathway. Further, in a sizeable dataset of human blood cell populations, tens of novel miRNAs and moRNAs were discovered, some of them with significantly varied expression levels among the cell types. Results demonstrate that miR&moRe2 is a valid tool for a comprehensive study of small RNAs generated from microRNA precursors and could help to investigate their biogenesis and function.
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