TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions

Kim, Daehwan; Pertea, Geo; Trapnell, Cole; Pimentel, Harold; Ryan, Katherine S.; Salzberg, Steven L.

doi:10.1186/gb-2013-14-4-r36

Cited by 11,435 publications

(9,354 citation statements)

References 18 publications

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“…Paired‐end reads were aligned to the human genome (hg19) using the splicing‐aware aligner Tophat2 (Kim et al , 2013). Duplicate reads were identified using the picard tools (1.98) script mark duplicates (https://github.com/broadinstitute/picard) and only non‐duplicate reads were retained.…”

Section: Methodsmentioning

confidence: 99%

Mitochondria are required for pro‐ageing features of the senescent phenotype

et al. 2016

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Cell senescence is an important tumour suppressor mechanism and driver of ageing. Both functions are dependent on the development of the senescent phenotype, which involves an overproduction of pro‐inflammatory and pro‐oxidant signals. However, the exact mechanisms regulating these phenotypes remain poorly understood. Here, we show the critical role of mitochondria in cellular senescence. In multiple models of senescence, absence of mitochondria reduced a spectrum of senescence effectors and phenotypes while preserving ATP production via enhanced glycolysis. Global transcriptomic analysis by RNA sequencing revealed that a vast number of senescent‐associated changes are dependent on mitochondria, particularly the pro‐inflammatory phenotype. Mechanistically, we show that the ATM, Akt and mTORC1 phosphorylation cascade integrates signals from the DNA damage response (DDR) towards PGC‐1β‐dependent mitochondrial biogenesis, contributing to a ROS‐mediated activation of the DDR and cell cycle arrest. Finally, we demonstrate that the reduction in mitochondrial content in vivo, by either mTORC1 inhibition or PGC‐1β deletion, prevents senescence in the ageing mouse liver. Our results suggest that mitochondria are a candidate target for interventions to reduce the deleterious impact of senescence in ageing tissues.

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Section: Methodsmentioning

confidence: 99%

Mitochondria are required for pro‐ageing features of the senescent phenotype

et al. 2016

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“…Mapping was carried out against the reference genome obtained from the Candida Genome Database [19]. We used the splice junction sensitive mapper Tophat 2.01.13 [32] with default settings, and mapped by applying the bowtie 2.2.4 [33] short read mapper. The counts per gene were estimated by using flux-capacitor [34].…”

Section: Methodsmentioning

confidence: 99%

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

et al. 2018

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Lipid mediators, derived from arachidonic acid metabolism, play an important role in immune regulation. The functions of bioactive eicosanoids range from modulating cytokine signaling and inflammasome formation to anti-inflammatory and pro-resolving activities. Human pathogenic fungi such as Candida albicans, Candida parapsilosis, Cryptococcus neoformans and Aspergillus fumigatus have been shown to produce such lipid mediators, associated with their virulence. To date, investigations into the molecular mechanisms of fungal eicosanoid biosynthesis in different species have revealed that several genes are associated with prostaglandin production. However, these routes remain uncharacterized in C. parapsilosis with early results suggesting it uses pathways distinct from those found in C. albicans. Therefore, we aimed to identify and characterize C. parapsilosis genes involved in eicosanoid biosynthesis. Following arachidonic acid treatment of C. parapsilosis cells, we identified several genes interfering with prostaglandin production. Out of the identified genes, homologues of a multi copper oxidase (FET3), an Acyl-CoA thiolase (POT1) and an Acyl-CoA oxidase (POX1-3) were found to play a significant role in prostaglandin synthesis. Furthermore, all three genes were confirmed to enhance C. parapsilosis pathogenicity, as the corresponding deletion mutants were cleared more efficiently by human macrophages and induced higher levels of pro-inflammatory cytokines. In addition, the mutants were less virulent than the wild-type strain in a mouse model of systemic infection. Taken together, we identified three genes that regulate eicosanoid biosynthesis in C. parapsilosis and impact the fungus’ virulence.

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“…For the analysis of differentially expressed genes (DEGs), the quality-checked reads for each condition were processed using the TopHat version 2.0.12 package (70). The reads were mapped to the reference genome ( Mus musculus Ensembl mm9 sequence), and the alignment files were generated as binary sequence alignment map (BAM) files.…”

Section: Methodsmentioning

confidence: 99%

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

et al. 2016

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The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations.

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TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions

Cited by 11,435 publications

References 18 publications

Mitochondria are required for pro‐ageing features of the senescent phenotype

Mitochondria are required for pro‐ageing features of the senescent phenotype

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

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