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Genome Biology

Daphne Tsoucas, Guo-Cheng Yuan
Single-cell analysis is a powerful tool for dissecting the cellular composition within a tissue or organ. However, it remains difficult to detect rare and common cell types at the same time. Here, we present a new computational method, GiniClust2, to overcome this challenge. GiniClust2 combines the strengths of two complementary approaches, using the Gini index and Fano factor, respectively, through a cluster-aware, weighted ensemble clustering technique. GiniClust2 successfully identifies both common and rare cell types in diverse datasets, outperforming existing methods...
May 10, 2018: Genome Biology
Laura Elnitski, Ivan Ovcharenko
Two recent studies explore how redundant enhancers in mice really are.
May 8, 2018: Genome Biology
Tom Aharon Hait, David Amar, Ron Shamir, Ran Elkon
Recent sequencing technologies enable joint quantification of promoters and their enhancer regions, allowing inference of enhancer-promoter links. We show that current enhancer-promoter inference methods produce a high rate of false positive links. We introduce FOCS, a new inference method, and by benchmarking against ChIA-PET, HiChIP, and eQTL data show that it results in lower false discovery rates and at the same time higher inference power. By applying FOCS to 2630 samples taken from ENCODE, Roadmap Epigenomics, FANTOM5, and a new compendium of GRO-seq samples, we provide extensive enhancer-promotor maps ( http://acgt...
May 1, 2018: Genome Biology
Angel-Carlos Román, Julián Vicente-Page, Alfonso Pérez-Escudero, Jose M Carvajal-González, Pedro M Fernández-Salguero, Gonzalo G de Polavieja
BACKGROUND: Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We use the zebrafish (Danio rerio) as a model to test the influence of histone modifications on behavior. RESULTS: We find that laboratory and isogenic zebrafish larvae show consistent individual behaviors when swimming freely in identical wells or in reaction to stimuli. This behavioral inter-individual variability is reduced when we impair the histone deacetylation pathway...
April 25, 2018: Genome Biology
Tingting Li, Lumeng Jia, Yong Cao, Qing Chen, Cheng Li
We develop a method called open chromatin enrichment and network Hi-C (OCEAN-C) for antibody-independent mapping of global open chromatin interactions. By integrating FAIRE-seq and Hi-C, OCEAN-C detects open chromatin interactions enriched by active cis-regulatory elements. We identify more than 10,000 hubs of open chromatin interactions (HOCIs) in human cells, which are mainly active promoters and enhancers bound by many DNA-binding proteins and form interaction networks crucial for gene transcription. In addition to identifying large-scale topological structures, including topologically associated domains and A/B compartments, OCEAN-C can detect HOCI-mediated chromatin interactions that are strongly associated with gene expression, super-enhancers, and broad H3K4me3 domains...
April 24, 2018: Genome Biology
Lynn Yi, Harold Pimentel, Nicolas L Bray, Lior Pachter
Compared to RNA-sequencing transcript differential analysis, gene-level differential expression analysis is more robust and experimentally actionable. However, the use of gene counts for statistical analysis can mask transcript-level dynamics. We demonstrate that 'analysis first, aggregation second,' where the p values derived from transcript analysis are aggregated to obtain gene-level results, increase sensitivity and accuracy. The method we propose can also be applied to transcript compatibility counts obtained from pseudoalignment of reads, which circumvents the need for quantification and is fast, accurate, and model-free...
April 12, 2018: Genome Biology
Cong Ma, Mingfu Shao, Carl Kingsford
Transcripts are frequently modified by structural variations, which lead to fused transcripts of either multiple genes, known as a fusion gene, or a gene and a previously non-transcribed sequence. Detecting these modifications, called transcriptomic structural variations (TSVs), especially in cancer tumor sequencing, is an important and challenging computational problem. We introduce SQUID, a novel algorithm to predict both fusion-gene and non-fusion-gene TSVs accurately from RNA-seq alignments. SQUID unifies both concordant and discordant read alignments into one model and doubles the precision on simulation data compared to other approaches...
April 12, 2018: Genome Biology
Bing Yao, Peng Jin
A new study reveals comprehensive and unique epigenetic properties of glioma stem cells, leading to novel molecular insights and therapeutic potentials toward glioblastoma multiforme treatment.
April 10, 2018: Genome Biology
Agata Wesolowska-Andersen, Jamie L Everman, Rebecca Davidson, Cydney Rios, Rachelle Herrin, Celeste Eng, William J Janssen, Andrew H Liu, Sam S Oh, Rajesh Kumar, Tasha E Fingerlin, Jose Rodriguez-Santana, Esteban G Burchard, Max A Seibold
In our recent article [1], it has come to our attention that the sample labels are not consistent between Table 1, the data labels deposited in the Sequence Read Archive, and Additional file 1: Table S2. We are therefore providing an updated Additional file 1: Table S2 so identical samples now have the same label.
April 10, 2018: Genome Biology
Hamid Beiki, Andrea L Eveland, Christopher K Tuggle
A report on the International Plant and Animal Genomes (PAG) conference held in San Diego, USA, 13-17 January 2018.
April 10, 2018: Genome Biology
Jessy Cartier, Thomas Smith, John P Thomson, Catherine M Rose, Batbayar Khulan, Andreas Heger, Richard R Meehan, Amanda J Drake
BACKGROUND: Early life exposure to adverse environments affects cardiovascular and metabolic systems in the offspring. These programmed effects are transmissible to a second generation through both male and female lines, suggesting germline transmission. We have previously shown that prenatal overexposure to the synthetic glucocorticoid dexamethasone (Dex) in rats reduces birth weight in the first generation (F1), a phenotype which is transmitted to a second generation (F2), particularly through the male line...
April 10, 2018: Genome Biology
Xiaoping Han, Haide Chen, Daosheng Huang, Huidong Chen, Lijiang Fei, Chen Cheng, He Huang, Guo-Cheng Yuan, Guoji Guo
BACKGROUND: Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved. RESULTS: We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells...
April 5, 2018: Genome Biology
Seyed Yahya Anvar, Guy Allard, Elizabeth Tseng, Gloria M Sheynkman, Eleonora de Klerk, Martijn Vermaat, Raymund H Yin, Hans E Johansson, Yavuz Ariyurek, Johan T den Dunnen, Stephen W Turner, Peter A C 't Hoen
BACKGROUND: The multifaceted control of gene expression requires tight coordination of regulatory mechanisms at transcriptional and post-transcriptional level. Here, we studied the interdependence of transcription initiation, splicing and polyadenylation events on single mRNA molecules by full-length mRNA sequencing. RESULTS: In MCF-7 breast cancer cells, we find 2700 genes with interdependent alternative transcription initiation, splicing and polyadenylation events, both in proximal and distant parts of mRNA molecules, including examples of coupling between transcription start sites and polyadenylation sites...
March 29, 2018: Genome Biology
Kevin C H Ha, Benjamin J Blencowe, Quaid Morris
Alternative polyadenylation (APA) affects most mammalian genes. The genome-wide investigation of APA has been hampered by an inability to reliably profile it using conventional RNA-seq. We describe 'Quantification of APA' (QAPA), a method that infers APA from conventional RNA-seq data. QAPA is faster and more sensitive than other methods. Application of QAPA reveals discrete, temporally coordinated APA programs during neurogenesis and that there is little overlap between genes regulated by alternative splicing and those by APA...
March 28, 2018: Genome Biology
Andreas J Gruber, Ralf Schmidt, Souvik Ghosh, Georges Martin, Andreas R Gruber, Erik van Nimwegen, Mihaela Zavolan
3' Untranslated regions (3' UTRs) length is regulated in relation to cellular state. To uncover key regulators of poly(A) site use in specific conditions, we have developed PAQR, a method for quantifying poly(A) site use from RNA sequencing data and KAPAC, an approach that infers activities of oligomeric sequence motifs on poly(A) site choice. Application of PAQR and KAPAC to RNA sequencing data from normal and tumor tissue samples uncovers motifs that can explain changes in cleavage and polyadenylation in specific cancers...
March 28, 2018: Genome Biology
Dan Zhou, Bonnie M Alver, Shuang Li, Ryan A Hlady, Joyce J Thompson, Mark A Schroeder, Jeong-Heon Lee, Jingxin Qiu, Philip H Schwartz, Jann N Sarkaria, Keith D Robertson
BACKGROUND: Glioma stem cells (GSCs) are a subpopulation of stem-like cells that contribute to glioblastoma (GBM) aggressiveness, recurrence, and resistance to radiation and chemotherapy. Therapeutically targeting the GSC population may improve patient survival, but unique vulnerabilities need to be identified. RESULTS: We isolate GSCs from well-characterized GBM patient-derived xenografts (PDX), characterize their stemness properties using immunofluorescence staining, profile their epigenome including 5mC, 5hmC, 5fC/5caC, and two enhancer marks, and define their transcriptome...
March 27, 2018: Genome Biology
Charles A Gersbach, Rodolphe Barrangou
Orthogonal CRISPR-Cas systems have been integrated into combinatorial screens to decipher complex genetic relationships in two recent studies.
March 26, 2018: Genome Biology
Gaetan Burgio
In the recent Research Highlight [1], it has been highlighted that part b of Fig. 1 was incorrectly labelled as "sgRNA + tracrRNA" instead of "sgRNA (crRNA + tracrRNA)". An updated Figure 1, including also the amended figure legend has therefore been provided below.
March 26, 2018: Genome Biology
Juan L Trincado, Juan C Entizne, Gerald Hysenaj, Babita Singh, Miha Skalic, David J Elliott, Eduardo Eyras
Despite the many approaches to study differential splicing from RNA-seq, many challenges remain unsolved, including computing capacity and sequencing depth requirements. Here we present SUPPA2, a new method that addresses these challenges, and enables streamlined analysis across multiple conditions taking into account biological variability. Using experimental and simulated data, we show that SUPPA2 achieves higher accuracy compared to other methods, especially at low sequencing depth and short read length...
March 23, 2018: Genome Biology
Yu Hong, Guangqing Lu, Jinzhi Duan, Wenjing Liu, Yu Zhang
CRISPR/dCas9 binds precisely to defined genomic sequences through targeting of guide RNA (gRNA) sequences. In vivo imaging of genomic loci can be achieved by recruiting fluorescent proteins using either dCas9 or gRNA. We thoroughly validate and compare the effectiveness and specificity of several dCas9/gRNA genome labeling systems. Surprisingly, we discover that in the gRNA-labeling strategies, accumulation of tagged gRNA transcripts leads to non-specific labeling foci. Furthermore, we develop novel bimolecular fluorescence complementation (BIFC) methods that combine the advantages of both dCas9-labeling and gRNA-labeling strategies...
March 22, 2018: Genome Biology
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