GFOLD: a generalized fold change for ranking differentially expressed genes from RNA-seq data

Feng, Jianxing; Meyer, Clifford A.; Wang, Qian; Liu, Jun S.; Liu, X. Shirley; Zhang, Yong

doi:10.1093/bioinformatics/bts515

Cited by 373 publications

(334 citation statements)

References 39 publications

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“…Approximately 20 million, 50 bp paired-end reads were generated for each sample. Quality filtered reads were mapped to the A. gambiae genome using the TopHat2 short read mapper (66) and quantified using generalized fold change (GFOLD) differential expression analysis program (67). Transcript abundance values were calculated for unmated and mated samples separately.…”

Section: Methodsmentioning

confidence: 99%

Odorant receptor-mediated sperm activation in disease vector mosquitoes

Pitts

Liu

Zhou

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Insects, such as the malaria vector mosquito, Anopheles gambiae, depend upon chemoreceptors to respond to volatiles emitted from a range of environmental sources, most notably blood meal hosts and oviposition sites. A subset of peripheral signaling pathways involved in these insect chemosensory-dependent behaviors requires the activity of heteromeric odorant receptor (OR) ion channel complexes and ligands for numerous A. gambiae ORs (AgOrs) have been identified. Although AgOrs are expressed in nonhead appendages, studies characterizing potential AgOr function in nonolfactory tissues have not been conducted. In the present study, we explore the possibility that AgOrs mediate responses of spermatozoa to endogenous signaling molecules in A. gambiae. In addition to finding AgOr transcript expression in testes, we show that the OR coreceptor, AgOrco, is localized to the flagella of A. gambiae spermatozoa where Orco-specific agonists, antagonists, and other odorant ligands robustly activate flagella beating in an Orco-dependent process. We also demonstrate Orco expression and Orco-mediated activation of spermatozoa in the yellow fever mosquito, Aedes aegypti. Moreover, we find Orco localization in testes across distinct insect taxa and posit that OR-mediated responses in spermatozoa may represent a general characteristic of insect reproduction and an example of convergent evolution.transcriptomics | cell signaling | gamete | chemical ecology | Culicidae

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Section: Methodsmentioning

confidence: 99%

Odorant receptor-mediated sperm activation in disease vector mosquitoes

Pitts

Liu

Zhou

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…27 Differentially expressed genes before and after AML1/ETO knockdown were detected by the GFOLD (generalized fold change) algorithm 28 (Version 1.0.9). The detailed analysis of the expression data of Kasumi-1 (GSE43834), 14 SKNO-1 (GSE34594), 20 and AML patients (GSE14468) 29 is available in supplemental Methods.…”

Section: Gene Expression Analysismentioning

confidence: 99%

Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia

Wang

et al. 2016

Blood

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Key Points• Wild-type AML1 and AML1/ ETO form a complex on chromatin via binding to adjacent different motifs and interacting through the runt homology domain.• The relative binding signals of AML1/ETO and AML1 and AP-1 recruitment determine whether AML1/ETO activates or represses its targets.The AML1/ETO fusion protein is essential to the development of t(8;21) acute myeloid leukemia (AML) and is well recognized for its dominant-negative effect on the coexisting wild-type protein AML1. However, the genome-wide interplay between AML1/ETO and wild-type AML1 remains elusive in the leukemogenesis of t(8;21) AML. Through chromatin immunoprecipitation sequencing and computational analysis, followed by a series of experimental validations, we report here that wild-type AML1 is able to orchestrate the expression of AML1/ETO targets regardless of being activated or repressed; this is achieved via forming a complex with AML1/ETO and via recruiting the cofactor AP-1 on chromatin. On chromatin occupancy, AML1/ETO and wild-type AML1 largely overlap and preferentially bind to adjacent and distinct short and long AML1 motifs on the colocalized regions, respectively. On physical interaction, AML1/ETO can form a complex with wild-type AML1 on chromatin, and the runt homology domain of both proteins are responsible for their interactions. More importantly, the relative binding signals of AML1 and AML1/ETO on chromatin determine which genes are repressed or activated by AML1/ETO. Further analysis of coregulators indicates that AML1/ETO transactivates gene expression through recruiting AP-1 to the AML1/ETO-AML1 complex. These findings enrich our knowledge of understanding the significance of the interplay between the wild-type protein and the oncogenic fusion protein in the development of leukemia. (Blood. 2016;127(2):233-242) IntroductionMany oncogenic fusion proteins generated by chromosomal translocations play a causal role in the development of leukemia. The oncogenic lesion almost exclusively occurs in a single allele within an individual leukemia, whereas the wild-type protein produced from the nontranslocated allele generally still exists.1,2 The coexistence of the wild-type protein with the oncogenic fusion protein raises the question about their significance in leukemogenesis. To address this question, acute myeloid leukemia (AML) with the t(8;21) translocation and resultant AML1/ETO fusion gene is an ideal model, particularly through understanding the interplay between the AML1/ETO fusion protein and the AML1 wild-type protein.AML1 (also known as RUNX1 or core-binding factor a [CBFa]), a critical regulator of normal hematopoiesis, 3 is widely expressed in multiple hematopoietic lineages and regulates the expression of a variety of hematopoietic genes through recognizing the motif TGTGGT.4 AML1 is frequently involved in chromosomal abnormalities in AML, [5][6][7] among which AML1/ETO is the most common fusion protein resulted from the t(8;21) translocation. 7 Structurally, AML1/ETO consists of the N-terminal portion o...

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“…2; ref. 34) increased or decreased levels in shCLK2-expressing cells implying global reprogramming of the transcriptome (Supplementary Table S4). Many of the most significantly downregulated genes encode for proteins with known roles in epithelial cell differentiation such as SPRR1A, SPRR1B, S100A7, S100A9.…”

Section: Clk2-mediated Changes In Gene Expression and Splicing Patternsmentioning

confidence: 99%

CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer

et al. 2015

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Genetically activated kinases have been attractive therapeutic targets in cancer due to the relative ease of developing tumorspecific treatment strategies for them. To discover novel putative oncogenic kinases, we identified 26 genes commonly amplified and overexpressed in breast cancer and subjected them to a lentiviral shRNA cell viability screen in a panel of breast cancer cell lines. Here, we report that CLK2, a kinase that phosphorylates SR proteins involved in splicing, acts as an oncogene in breast cancer. Deregulated alternative splicing patterns are commonly observed in human cancers but the underlying mechanisms and functional relevance are still largely unknown. CLK2 is amplified and overexpressed in a significant fraction of breast tumors. Downregulation of CLK2 inhibits breast cancer growth in cell culture and in xenograft models and it enhances cell migration and invasion. Loss of CLK2 in luminal breast cancer cells leads to the upregulation of epithelial-to-mesenchymal transition (EMT)-related genes and a switch to mesenchymal splice variants of several genes, including ENAH (MENA). These results imply that therapeutic targeting of CLK2 may be used to modulate EMT splicing patterns and to inhibit breast tumor growth. Cancer Res; 75(7); 1516-26.Ó2015 AACR.

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GFOLD: a generalized fold change for ranking differentially expressed genes from RNA-seq data

Abstract: The open source C/C++ program is available at http://www.tongji.edu.cn/∼zhanglab/GFOLD/index.html

Cited by 373 publications

References 39 publications

Odorant receptor-mediated sperm activation in disease vector mosquitoes

Odorant receptor-mediated sperm activation in disease vector mosquitoes

Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia

CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer

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