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Genome Biology

A P Lipinska, M L Serrano-Serrano, A Cormier, A F Peters, K Kogame, J M Cock, S M Coelho
BACKGROUND: Sexual life cycles in eukaryotes involve a cyclic alternation between haploid and diploid phases. While most animals possess a diploid life cycle, many plants and algae alternate between multicellular haploid (gametophyte) and diploid (sporophyte) generations. In many algae, gametophytes and sporophytes are independent and free-living and may present dramatic phenotypic differences. The same shared genome can therefore be subject to different, even conflicting, selection pressures during each of the life cycle generations...
February 14, 2019: Genome Biology
Shahab Sarmashghi, Kristine Bohmann, M Thomas P Gilbert, Vineet Bafna, Siavash Mirarab
The ability to inexpensively describe taxonomic diversity is critical in this era of rapid climate and biodiversity changes. The recent genome-skimming approach extends current barcoding practices beyond short markers by applying low-pass sequencing and recovering whole organelle genomes computationally. This approach discards the nuclear DNA, which constitutes the vast majority of the data. In contrast, we suggest using all unassembled reads. We introduce an assembly-free and alignment-free tool, Skmer, to compute genomic distances between the query and reference genome skims...
February 13, 2019: Genome Biology
Domenico Alessandro Silvestris, Ernesto Picardi, Valeriana Cesarini, Bruno Fosso, Nicolò Mangraviti, Luca Massimi, Maurizio Martini, Graziano Pesole, Franco Locatelli, Angela Gallo
BACKGROUND: Adenosine-to-inosine (A-to-I) RNA editing is an essential post-transcriptional mechanism mediated by ADAR enzymes that have been recently associated with cancer. RESULTS: Here, we characterize the inosinome signature in normal brain and de novo glioblastoma (GBM) using new metrics that re-stratify GBM patients according to their editing profiles and indicate this post-transcriptional event as a possible molecular mechanism for sexual dimorphism in GBM...
February 13, 2019: Genome Biology
Barthélémy Caron, Yufei Luo, Antonio Rausell
State-of-the-art methods assessing pathogenic non-coding variants have mostly been characterized on common disease-associated polymorphisms, yet with modest accuracy and strong positional biases. In this study, we curated 737 high-confidence pathogenic non-coding variants associated with monogenic Mendelian diseases. In addition to interspecies conservation, a comprehensive set of recent and ongoing purifying selection signals in humans is explored, accounting for lineage-specific regulatory elements. Supervised learning using gradient tree boosting on such features achieves a high predictive performance and overcomes positional bias...
February 11, 2019: Genome Biology
Kenta Sato, Koki Tsuyuzaki, Kentaro Shimizu, Itoshi Nikaido
Recent technical improvements in single-cell RNA sequencing (scRNA-seq) have enabled massively parallel profiling of transcriptomes, thereby promoting large-scale studies encompassing a wide range of cell types of multicellular organisms. With this background, we propose CellFishing.jl, a new method for searching atlas-scale datasets for similar cells and detecting noteworthy genes of query cells with high accuracy and throughput. Using multiple scRNA-seq datasets, we validate that our method demonstrates comparable accuracy to and is markedly faster than the state-of-the-art software...
February 11, 2019: Genome Biology
Stephanie M Linker, Lara Urban, Stephen J Clark, Mariya Chhatriwala, Shradha Amatya, Davis J McCarthy, Ingo Ebersberger, Ludovic Vallier, Wolf Reik, Oliver Stegle, Marc Jan Bonder
BACKGROUND: Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic features, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remains poorly understood...
February 11, 2019: Genome Biology
Caroline Pont, Stefanie Wagner, Antoine Kremer, Ludovic Orlando, Christophe Plomion, Jerome Salse
How contemporary plant genomes originated and evolved is a fascinating question. One approach uses reference genomes from extant species to reconstruct the sequence and structure of their common ancestors over deep timescales. A second approach focuses on the direct identification of genomic changes at a shorter timescale by sequencing ancient DNA preserved in subfossil remains. Merged within the nascent field of paleogenomics, these complementary approaches provide insights into the evolutionary forces that shaped the organization and regulation of modern genomes and open novel perspectives in fostering genetic gain in breeding programs and establishing tools to predict future population changes in response to anthropogenic pressure and global warming...
February 11, 2019: Genome Biology
Tracy J Ballinger, Britta A M Bouwman, Reza Mirzazadeh, Silvano Garnerone, Nicola Crosetto, Colin A Semple
BACKGROUND: Structural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. Many SVs are thought to emerge from errors in the repair processes following DNA double strand breaks (DSBs). RESULTS: We used experimentally quantified DSB frequencies in cell lines with matched chromatin and sequence features to derive the first quantitative genome-wide models of DSB susceptibility...
February 8, 2019: Genome Biology
Emanuel Gonçalves, Fiona M Behan, Sandra Louzada, Damien Arnol, Euan A Stronach, Fengtang Yang, Kosuke Yusa, Oliver Stegle, Francesco Iorio, Mathew J Garnett
BACKGROUND: CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functional consequences of CRISPR-Cas9 gene-editing has not yet been assessed. RESULTS: Utilizing CRISPR-Cas9 knockout screens for 250 cancer cell lines, we demonstrate that targeting structurally rearranged regions, in particular tandem or interspersed amplifications, is highly detrimental to cellular fitness in a gene-independent manner...
February 5, 2019: Genome Biology
Fei Teng, Jing Li, Tongtong Cui, Kai Xu, Lu Guo, Qingqin Gao, Guihai Feng, Chuanyuan Chen, Dali Han, Qi Zhou, Wei Li
CRISPR-Cas12a/Cpf1, a single RNA-guided endonuclease system, provides a promising tool for genome engineering. However, only three Cas12a orthologs have been employed for mammalian genome editing, and the editing efficiency as well as targeting coverage still requires improvements. Here, we harness six novel Cas12a orthologs for genome editing in human and mouse cells, some of which utilize simple protospacer adjacent motifs (PAMs) that remarkably increase the targeting range in the genomes. Moreover, we identify optimized CRISPR RNA (crRNA) scaffolds that can increase the genome editing efficiency of Cas12a...
February 5, 2019: Genome Biology
Shuhua Fu, Anqi Wang, Kin Fai Au
BACKGROUND: Third-generation sequencing technologies have advanced the progress of the biological research by generating reads that are substantially longer than second-generation sequencing technologies. However, their notorious high error rate impedes straightforward data analysis and limits their application. A handful of error correction methods for these error-prone long reads have been developed to date. The output data quality is very important for downstream analysis, whereas computing resources could limit the utility of some computing-intense tools...
February 4, 2019: Genome Biology
Ni A An, Wanqiu Ding, Xin-Zhuang Yang, Jiguang Peng, Bin Z He, Qing Sunny Shen, Fujian Lu, Aibin He, Yong E Zhang, Bertrand Chin-Ming Tan, Jia-Yu Chen, Chuan-Yun Li
BACKGROUND: Recent studies have revealed thousands of A-to-I RNA editing events in primates, but the origination and general functions of these events are not well addressed. RESULTS: Here, we perform a comparative editome study in human and rhesus macaque and uncover a substantial proportion of macaque A-to-I editing sites that are genomically polymorphic in some animals or encoded as non-editable nucleotides in human. The occurrence of these recent gain and loss of RNA editing through DNA point mutation is significantly more prevalent than that expected for the nearby regions...
February 4, 2019: Genome Biology
Michael C Schatz, Andrew Cosgrove
No abstract text is available yet for this article.
February 1, 2019: Genome Biology
Nur Diana Anuar, Sebastian Kurscheid, Matt Field, Lei Zhang, Edward Rebar, Philip Gregory, Thierry Buchou, Josephine Bowles, Peter Koopman, David J Tremethick, Tatiana A Soboleva
BACKGROUND: Altering the biochemical makeup of chromatin by the incorporation of histone variants during development represents a key mechanism in regulating gene expression. The histone variant H2A.B, H2A.B.3 in mice, appeared late in evolution and is most highly expressed in the testis. In the mouse, it is encoded by three different genes. H2A.B expression is spatially and temporally regulated during spermatogenesis being most highly expressed in the haploid round spermatid stage. Active genes gain H2A...
January 31, 2019: Genome Biology
Xutong Wang, Liyang Chen, Jianxin Ma
BACKGROUND: Evidence of introgression, the transfer of genetic material, between crops and their wild relatives through spontaneous hybridization and subsequent backcrossing has been documented; however, the evolutionary patterns and consequences of introgression and its influence on the processes of crop domestication and varietal diversification are poorly understood. RESULTS: We investigate the genomic landscape and evolution of putative crop-wild-relative introgression by analyzing the nuclear and chloroplast genomes from a panel of wild (Glycine soja) and domesticated (Glycine max) soybeans...
January 30, 2019: Genome Biology
Jean-Philippe Fortin, Jenille Tan, Karen E Gascoigne, Peter M Haverty, William F Forrest, Michael R Costa, Scott E Martin
BACKGROUND: Genome-wide loss-of-function screens using the CRISPR/Cas9 system allow the efficient discovery of cancer cell vulnerabilities. While several studies have focused on correcting for DNA cleavage toxicity biases associated with copy number alterations, the effects of sgRNAs co-targeting multiple genomic loci in CRISPR screens have not been discussed. RESULTS: In this work, we analyze CRISPR essentiality screen data from 391 cancer cell lines to characterize biases induced by multi-target sgRNAs...
January 25, 2019: Genome Biology
Shiyou Zhu, Zhongzheng Cao, Zhiheng Liu, Yuan He, Yinan Wang, Pengfei Yuan, Wei Li, Feng Tian, Ying Bao, Wensheng Wei
We report a new method using re-designed guide RNAs with internal barcodes (iBARs) embedded in their loop regions. Our iBAR approach outperforms the conventional method by producing screening results with much lower false-positive and false-negative rates especially with a high multiplicity of infection (MOI). Importantly, the iBAR approach reduces the starting cells at high MOI significantly with greatly improved efficiency and accuracy compared with the canonical CRISPR screens at a low MOI. This new system is particularly useful when the source of cells is limited or when it is difficult to control viral infection for in vivo screening...
January 24, 2019: Genome Biology
Xiao Chen, Mi Liu, Hongyan Lou, Yiyi Lu, Meng-Tao Zhou, Rongying Ou, Yunsheng Xu, Kai-Fu Tang
Trim-Away is a recent technique to rapidly deplete a protein from any cell type. Guided by antibodies, TRIM21 selects proteins for destruction. However, the applicability of this method in model organisms has not been investigated. Here, we show that Trim-Away can degrade proteins in zebrafish embryos. Trim-Away depletes proteins faster than morpholinos, which enables analysis of protein function during early embryogenesis. Furthermore, Trim-Away can be applied to evaluate the role of maternally contributed proteins in zebrafish embryos...
January 23, 2019: Genome Biology
Barbara Cheifet
We polled the Editorial Board of Genome Biology to ask where they see genomics going in the next few years. Here are some of their responses.
January 22, 2019: Genome Biology
Weijun Liu, Xiaowei Wang
We perform a large-scale RNA sequencing study to experimentally identify genes that are downregulated by 25 miRNAs. This RNA-seq dataset is combined with public miRNA target binding data to systematically identify miRNA targeting features that are characteristic of both miRNA binding and target downregulation. By integrating these common features in a machine learning framework, we develop and validate an improved computational model for genome-wide miRNA target prediction. All prediction data can be accessed at miRDB ( http://mirdb...
January 22, 2019: Genome Biology
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