跳到主要內容

臺灣博碩士論文加值系統

(3.235.227.117) 您好!臺灣時間:2021/07/28 01:41
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:歐佳怡
研究生(外文):Ou.Chiai
論文名稱:全基因體關聯性分析中檢測對偶基因專一性表現之統計架構
論文名稱(外文):A Statistical Framework For Testing Hypotheses Of Allele-Specific Expression In Genome-Wide Association Studies
指導教授:黃耀廷
指導教授(外文):Huang,Yaoting
口試委員:陳健尉林崇熙黃耀廷
口試委員(外文):Chen,ChienweiLin,ChonghsiHuang,Yaoting
口試日期:2012-07-31
學位類別:碩士
校院名稱:國立中正大學
系所名稱:資訊工程研究所
學門:工程學門
學類:電資工程學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:39
中文關鍵詞:核醣核酸序列基因表現量的差異對偶基因專一性表現對偶基因專一性表現量差異的基因
外文關鍵詞:RNA-SeqDifferential expression geneAllele-specific expressionAllele-specific differential expression gene
相關次數:
  • 被引用被引用:0
  • 點閱點閱:424
  • 評分評分:
  • 下載下載:4
  • 收藏至我的研究室書目清單書目收藏:0
在最近幾年來,由於高產量和低成本,大規模的平行定序技術正迅速成為有吸引力的取代芯片在全基因體關聯性疾病研究中的基因表現量。目前已經幾種方法是利用核醣核酸序列來比較生病和沒有生病的人之間基因表現量(稱為基因表現量的差異,DEG). 這些統計方法利用每個基因上核醣核酸序列條數來評估基因表現量差異的重要性。然而異常對偶基因專一性表現與一些人類的疾病有密切的相關。目前存在的一些演算法他們都沒有辦法區分生病的人和沒有生病的人之間的父系和母系的對偶基因專一性表現量差異(稱為對偶基因專一性表現量差異的基因,ASDEG)。在這一篇論文中,我們設計了一個統計的框架來找出生病和沒有生病的人之間對偶基因專一性表現量差異的基因,稱之為ASDEGdetector。實驗結果顯示,ASDEGdetector的靈敏性和特異性都比之前的方法都來的高。ASDEGdetector 在對於研究疾病和對偶基因專一性表現量差異的基因之間的關係是非常的有幫助的。
In the recent years, due to increasing throughput and decreasing cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide association study of gene expression in disease studies. Several methods have used RNA-seq for comparing gene expression between treatment and control groups (called differential expression gene, DEG). These statistical methods have been developed for assessing the significance of DEGs using total read counts of a gene. However, abnormal allele specific expression (ASE) is strongly associated with several human diseases. Existing algorithms are unable to distinguish the difference of paternal/maternal ASE between treatment and control groups (called allele specific differential expression gene, ASDEG). In this thesis, we designed and implemented a statistical framework called ASDEGdetector for finding allele-specific differential expression genes (ASDEG) between treatment and control groups. The experimental results indicated that the sensitivity and specificity of ASDEGdetector is much higher than previous methods.And ASDEGdetector is very useful for studying the linkage of disease and allele-specific differential expression.
1 Introduction 1
2 Literature Review 4
2.1 Introduction to RNA sequencing . . . . . . . . . . . . . . . . . . . 4
2.2 Introduction to Single Nucleotide Polymorphism . . . . . . . . . . 5
2.3 Introduction to Fisher Exact Test . . . . . . . . . . . . . . . . . . 6
2.4 Introduction to Combined P-value Method . . . . . . . . . . . . . 8
2.5 Introduction to FDR correction . . . . . . . . . . . . . . . . . . . 9
3 Material and Method 11
3.1 Estimation of the Allele-Specific Read Count . . . . . . . . . . . . 12
3.2 A Test of Association between Treatment and Control at Single
SNP Site . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.3 Combination of P-values . . . . . . . . . . . . . . . . . . . . . . . 15
3.3.1 Fisher’s Method . . . . . . . . . . . . . . . . . . . . . . . . 15
3.3.2 Stouffer’s Method . . . . . . . . . . . . . . . . . . . . . . . 16
3.3.3 Intersection Union Test . . . . . . . . . . . . . . . . . . . . 16
3.4 False Discovery Rate Correction . . . . . . . . . . . . . . . . . . . 17
3.5 Extension of Proposed Test Procedure to Multiple Samples . . . . 17
3.5.1 Sufficient Statistic . . . . . . . . . . . . . . . . . . . . . . . 18
3.5.2 Meta-Analysis of Treatment-Control Pairs . . . . . . . . . 18
4 Results and Discussion 21
4.1 Comparison of Various SNP rate . . . . . . . . . . . . . . . . . . 22
4.2 Comparison of Various fold change . . . . . . . . . . . . . . . . . 23
4.3 Results on multiple samples . . . . . . . . . . . . . . . . . . . . . 24
4.4 Results on Real Data Sets . . . . . . . . . . . . . . . . . . . . . . 25
5 Conclusion and Future Works 26
5.1 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
5.2 Future Works . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
[1] Anders, S. and Huber, W. Differential expression analysis for sequence count data. Genome Biol, 11(10):R106, 2010.
[2] Benjamini Y. and Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Methodological, 57:289–300, 1995.
[3] Bullard, J.H., Purdom, E., Hansen, K.D., et al. Evaluation of statistical methods for normalization and differential expression in mrna-seq experiments. BMC Bioinformatics, 11:94, 2010.
[4] Chiang, D.Y., Getz, G., Jaffe, D.B., et al. High-resolution mapping of copynumber alterations with massively parallel sequencing. Nature Methods, 6:99–103, 2009.
[5] Cowles, C.R., Hirschhorn, J.N., Altshuler, D., et al. Detection of regulatory variation in mouse genes. Nat Genet, 32(3):432–437, Nov 2002.
[6] Dalca, A.V. and Brudno, M. Genome variation discovery with high-throughput sequencing data. Brief Bioinform, 11(1):3–14, Jan 2010.
[7] Darlington, R. B. and Hayes, A. F. Combining independent p values: extensions of the stouffer and binomial methods. Psychol Methods, 5(4):496–515, Dec 2000.
[8] Frazer, K.A., Ballinger, D.G., Cox, D.R., et al. A second generation human haplotype map of over 3.1 million snps. Nature, 449(7164):851–861, Oct 2007.
[9] Hess, A. and Iyer, H. Fisher’s combined p-value for detecting differentially expressed genes using affymetrix expression arrays. BMC Genomics, 8:96, 2007.
[10] Hoehe, M.R., Kpke, K.,Wendel, B., et al. Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence. Hum Mol Genet, 9(19):2895–2908, Nov 2000.
[11] Kim, J. and Bartel, D.P. Allelic imbalance sequencing reveals that single nucleotide polymorphisms frequently alter microrna-directed repression. Nat Biotechnol, 27(5):472–477, May 2009.
[12] Klaus, S., Frank, B., and Yosef, H. Compatible confidence intervals for
intersection union tests involving two hypotheses. Monograph Series, 47:129–142, 2004.
[13] Knight, J.C., Keating, B.J., Rockett, K.A., et al. In vivo characterization of regulatory polymorphisms by allele-specific quantification of rna polymerase loading. Nat Genet, 33(4):469–475, Apr 2003.
[14] Li, H., Handsaker, B., Wysoker, A., et al. . The sequence alignment/map format and samtools. Bioinformatics, 25(16):2078–2079, Aug 2009.
[15] Lo, H.S., Wang, Z., Hu, Y., et al. . Allelic variation in gene expression is common in the human genome. Genome Res, 13(8):1855–1862, Aug 2003.
[16] Mannens,M. et al. Parental imprinting of human chromosome region 11p15.3-pter involved in the beckwithvwiedemann syndrome and various human neoplasia. Eur. J. Hum. Genet, 2:3–23, 1994.
[17] Mardis, E.R. The impact of next-generation sequencing technology on genetics. Trends Genet, 24(3):133–141, Mar 2008.
[18] Nicholls, R.D., Knepper, J.L. Genome organization, function, and imprinting in prader-willi and angelman syndromes. Annu. Rev. Genomics Hum. Genet., 2:153V175, 2001.
[19] Ogawa,O. et al. Relaxation of insulin-like growth factor ii gene imprintining implicated in wilms tumour. Nature, 362:749V751, 1993.
[20] Oshlack, A., Robinson, M.D., and Young, M.D. High-resolution mapping of copynumber alterations with massively parallel sequencing. Genome Biol, 11(12):220, 2010.
[21] Pant, P.V.K., Tao, H., Beilharz, E.J., et al. Analysis of allelic differential expression in human white blood cells. Genome Res, 16(3):331–339, Mar 2006.
[22] Pastinen, T. and Hudson, T.J. Cis-acting regulatory variation in the human genome. Science, 306(5696):647–650, Oct 2004.
[23] Pollard, K.S., Serre, D., Wang, X., et al. A genome-wide approach to identifying novel-imprinted genes. Hum Genet, 122(6):625–634, Jan 2008.
[24] R. A. Fisher. On the mathematical foundations of theoretical statistics. Philosophical Transactions of the Royal Society of London. Series A, Containing Papers of a Mathematical or Physical Character, 222:309–368, 1922.
[25] Rainier,S. et al. Relaxation of imprinted genes in human cancer. Nature, 362:747V749, 1993.
[26] Roberts, A., Pimentel, H., Trapnell, C., et al. Identification of novel transcripts in annotated genomes using rna-seq. Bioinformatics, 27(17):2325–2329, Sep 2011.
[27] Ronald, J., Akey, J.M., Whittle, J., et al. . Simultaneous genotyping, gene-expression measurement, and detection of allele-specific expression with oligonucleotide arrays. Genome Res, 15(2):284–291, Feb 2005.
[28] Ronald, J., Brem, R.B., Whittle, J., et al. Local regulatory variation in saccharomyces cerevisiae. PLoS Genet, 1(2):e25, Aug 2005.
[29] Serre, D., Gurd, S., Ge, B., et al. Differential allelic expression in the human genome: a robust approach to identify genetic and epigenetic cis-acting mechanisms regulating gene expression. PLoS Genet, 4(2):e1000006, Feb 2008.
[30] Shendure, J., Mitra, R.D., Varma, C., et al. Advanced sequencing technologies: methods and goals. Nat Rev Genet, 5(5):335–344, May 2004.
[31] Terwilliger, J.D., and Weiss, K.M. Linkage disequilibrium mapping of complex disease : fantasy or reality? Current Opinion in Biotechnology, 9:578V594, 1998.
[32] Trapnell, C., Pachter, L., and Salzberg, S.L. Tophat: discovering splice junctions with rna-seq. Bioinformatics, 25(9):1105–1111, May 2009.
[33] Tuch, B.B., Laborde, R.R., et al. Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations. PLoS One, 5(2):e9317, 2010.
[34] Voelkerding, K.V., Dames, S.A., and Durtschi, J.D. Next-generation sequencing: from basic research to diagnostics. Clin Chem, 55(4):641–658, Apr 2009.
[35] Wilkinson, L.S., Davies, W. and Isles, A.R. Genomic imprinting effects on brain development and function. Nat Rev Neurosci, 8(11):832–843, Nov 2007.
[36] Wittkopp, P.J., Haerum, B.K. and Clark, A.G. Evolutionary changes in cis and trans gene regulation. Nature, 430(6995):85–88, Jul 2004.
[37] Yang, H.H., Hu, Y., Edmonson, M., et al. Computation method to identify differential allelic gene expression and novel imprinted genes. Bioinformatics, 19(8):952–955, May 2003.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top