基于中值的JS散度可變剪接差異分析研究

劉文斌; 王兵; 方剛; 石曉龍; 許鵬

doi:10.11999/JEIT190941

基于中值的JS散度可變剪接差異分析研究

doi: 10.11999/JEIT190941 cstr: 32379.14.JEIT190941

劉文斌^{1, 2, ,},
王兵¹,
方剛²,
石曉龍²,
許鵬^{2, 3}

1.
溫州大學(xué)計(jì)算機(jī)與人工智能學(xué)院溫州 325035
2.
廣州大學(xué)計(jì)算科技研究院廣州 510006
3.
黔南民族師范學(xué)院計(jì)算機(jī)與信息學(xué)院都勻 558000

基金項(xiàng)目: 國(guó)家重點(diǎn)研發(fā)計(jì)劃(2019YFA0706402)，國(guó)家自然科學(xué)基金(61572367, 61573017, 61972107, 61972109)

詳細(xì)信息

作者簡(jiǎn)介:
劉文斌：男，1969年生，教授，研究方向?yàn)樯镄畔W(xué)

王兵：男，1993年生，碩士生，研究方向?yàn)樯镄畔W(xué)

方剛：男，1969年生，教授，研究方向?yàn)樯镄畔W(xué)

石曉龍：男，1975年生，教授，研究方向?yàn)樯镄畔W(xué)

許鵬：男，1986年生，博士后，研究方向?yàn)樯镄畔W(xué)

通訊作者:
劉文斌　wbliu6910@126.com

中圖分類號(hào): TP391
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- 文章訪問(wèn)數(shù): 1975
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- 被引次數(shù): 0
出版歷程
- 收稿日期: 2019-11-22
- 修回日期: 2020-04-24
- 網(wǎng)絡(luò)出版日期: 2020-05-13
- 刊出日期: 2020-06-22

Study on the Differential Analysis of Alternative Splicing Based on the Median Value Jensen-Shannon Divergence

Wenbin LIU^{1, 2
, ,},
Bing WANG¹,
Gang FANG²,
Xiaolong SHI²,
Peng XU^{2, 3}

1.
College of Computer Science and Artificial Intelligence, Wenzhou University, Wenzhou 325035, China
2.
Institute of Computing Science and Technology, Guangzhou University, Guangzhou 510006, China
3.
School of Computer Science and Information Technology, Qiannan Normal University for Nationalities, Duyun 558000, China

Funds: The National Key R&D Program of China (2019YFA0706402), The National Natural Science Foundation of China (61572367, 61573017, 61972107, 61972109)

摘要

摘要: 可變剪接是一種廣泛存在于生物體中造成蛋白質(zhì)多樣性的重要機(jī)制，它對(duì)細(xì)胞的增殖、分化、發(fā)育、凋亡等一系列重要的生物過(guò)程具有重要精細(xì)調(diào)控的作用。近年來(lái)，人們發(fā)現(xiàn)多種復(fù)雜疾病的產(chǎn)生往往伴隨著剪接異構(gòu)體的紊亂表達(dá)。為了研究剪接異構(gòu)體在整體分布上的差異，該文提出一種基于中值的JS散度可變剪接(AS)差異分析方法。結(jié)果表明，該文的方法能夠發(fā)現(xiàn)大量在剪接異構(gòu)體整體分布上具有顯著差異的基因。這些基因不僅富集在一些癌癥密切相關(guān)的通路，而且也富集在一些基于可變剪接調(diào)控的信號(hào)通路、細(xì)胞分裂過(guò)程和蛋白質(zhì)功能等通路。此外，與基因?qū)哟蔚牟町惙治鱿啾?，可變剪接顯著差異的基因在生存分析方面也具有更好的性能?？傊?，該文提出基于中值的JS散度可變剪接差異分析方法，將為進(jìn)一步揭示可變剪接在癌癥中的機(jī)制奠定基礎(chǔ)。
- 可變剪接 /
- 癌癥 /
- JS散度 /
- KEGG通路 /
- 驅(qū)動(dòng)基因
Abstract: Alternative splicing is an important mechanism of protein diversity in a wide range of organisms, which plays an important role in the fine regulation of cell proliferation, differentiation, development, apoptosis and a series of important biological processes. In recent years, it is found that the occurrence of multiple complex diseases is often accompanied by the disordered expression of splicing isoforms. In order to study the difference of splicing isoforms on the whole distribution, a differential analysis method of Alternative Splicing (AS) based on the median value by Jensen-Shannon (JS) divergence is proposed in this paper. The results show the method can finds plenty of genes with significant differences in the overall distribution of splicing isoforms. These genes are not only concentrated in some cancer related pathways, but also in some signaling pathways based on alternative splicing regulation, cell division process and protein function. In addition, compared with the gene-level differential analysis, the genes with significant difference in alternative splicing also have better performance in survival analysis. In conclusion, the proposed method will lay a foundation for further revealing the mechanism of alternative splicing in cancer.
- Alternative splicing /
- Cancer /
- Jensen-Shannon (JS) divergence /
- Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway /
- Driver gene

HTML全文

圖 1 4種方法差異基因的韋恩圖

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圖 2 乳腺癌驅(qū)動(dòng)基因的PPI網(wǎng)絡(luò)

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圖 3 癌癥分類結(jié)果比較

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圖 4 差異基因生存分析曲線

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表 1 癌癥數(shù)據(jù)集統(tǒng)計(jì)信息

癌癥	癌癥樣本	正常樣本	基因個(gè)數(shù)	異構(gòu)體個(gè)數(shù)
BRCA	1100	112	10178	33481
LIHC	373	50	8871	26234
UCEC	117	24	9765	30953

下載: 導(dǎo)出CSV

表 2 KEGG通路分析

癌癥	通路(Gen Model)	通路(AS Model)
	Focal adhesion	Cell cycle
	PI3K-Akt signaling pathway	p53 signaling pathway
	Tight junction	Pathways in cancer
	Regulation of lipolysis in adipocytes	Oocyte meiosis
BRCA	Pathways in cancer	Viral carcinogenesis
	Rap1 signaling pathway	Adherens junction
	cAMP signaling pathway	Purine metabolism
	ABC transporters	PI3K-Akt signaling pathway
	Cell adhesion molecules (CAMs)	Hippo signaling pathway
	Leukocyte transendothelial migration	Metabolic pathways
	Metabolic pathways	Metabolic pathways
	Fatty acid degradation	Phagosome
	Protein processing in endoplasmic reticulum	Fc gamma R-mediated phagocytosis
	Proteasome	Leishmaniasis
LIHC	mTOR signaling pathway	Homologous recombination
	AMPK signaling pathway	Sphingolipid metabolism
	Valine, leucine and isoleucine degradation	ECM-receptor interaction
	Spliceosome	Cell cycle
	Ubiquitin mediated proteolysis	Fanconi anemia pathway
	Insulin signaling pathway	Ribosome biogenesis in eukaryotes
	Vascular smooth muscle contraction	Osteoclast differentiation
	cGMP-PKG signaling pathway	Cell cycle
	Focal adhesion	Adherens junction
	MAPK signaling pathway	Axon guidance
UCEC	Proteoglycans in cancer	Phagosome
	Calcium signaling pathway	Rheumatoid arthritis
	Platelet activation	AMPK signaling pathway
	Adherens junction	PPAR signaling pathway
	Oxytocin signaling pathway	ECM-receptor interaction
	Ras signaling pathway	Platelet activation

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參考文獻(xiàn)(21)

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