利用大腸桿菌蛋白質體晶片分析新生兒血液中的免疫球蛋白

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姓名

王利民(Li-Ming Wang) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

利用大腸桿菌蛋白質體晶片分析新生兒血液中的免疫球蛋白
(Infant serum immunoglobulin analysis using Escherichia coli proteome microarrays)

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摘要(中)

免疫球蛋白又被稱作抗體，在人體的免疫系統中扮演著重要的角色。許多的研究利用抗體在血液中的濃度變化來預測相關疾病的發生。同時，也有許多文獻指出血液中抗體的濃度會隨著年齡的增長而有所變化。迄今，會與抗體所結合的蛋白質卻尚未以有效率且可靠的方式來被識別出。因此，我們利用高通量大腸桿菌蛋白質晶片與生物資訊的分析來探討被抗體所結合的蛋白質在生物功能上的作用為何。首先，我們將健康新生兒與成人的血清稀釋後佈滿到大腸桿菌蛋白質體晶片上，然後將代表信號強度的數據正規化，正規化過後的數據再以BiNGO結合Cytoscape與Gene Ontology資料庫來進行生物功能上的分析。我們的結果指出，在高免疫的族群中，大部分會與抗體結合的蛋白質都是屬於細胞內部的蛋白質；在低免疫的族群中，大部分會與抗體結合的蛋白質則是屬於膜蛋白。再者，會與IgA及IgM所結合的蛋白質，在生物功能上大部份是參與新陳代謝的反應，而會與IgG所結合的蛋白質，則大部份是屬於巨分子複合物。上面的結果意謂著不同的抗體對於不同功能性的蛋白質會有特定的專一性；換句話說，抗體在清除病原體時，是利用特定的抗體作用在病原體中特定功能的蛋白質上，進而破壞病原體在人體體內中存活的機能。

摘要(英)

Immunoglobulin is also known as antibody, it plays an important role in human adaptive immune system. Many researches predicted the human diseases by observing the significant changes of the antibody’s concentration. Moreover, several of scientific literatures showed the development of the antibody’s concentration during each different growing age in human serum. So far, the antibody binding proteins and their enriched functionality have not been identified. For this reason, we applied the E. coli proteome microarray and bioinformatics analysis to identify the antibody binding proteins and their biological functionalities in a fast and high-throughput technique. We probed infant and adult sera with E. coli proteome microarrays, and then normalized the numerical data. The normalized data were analyzed by the BiNGO plug-in Cytoscape based on Gene Ontology (GO) database. The results of the BiNGO analysis showed that the antibody binding proteins were intracellular if they had highly signal intensity in highly immunogenic samples, otherwise the antibody binding proteins were membrane protein. Furthermore, IgA and IgM binding proteins were associated with metabolic process, and IgG binding proteins were associated with macromolecular complex in highly immunogenic samples. The results suggest that each antibody profiling have a specific target of protein’s functionality by using the E. coli proteome microarray and combined with the bioinformatics analysis, so the pathogens would be eliminated by different antibodies interact with their specific functionality on antigens of pathogen’s proteins.

關鍵字(中)

★ 新生兒
★ 血清
★ 免疫球蛋白
★ 免疫系統
★ 蛋白質體晶片
★ 抗體

關鍵字(英)

★ Immunoglobulin
★ Immune system
★ Antibody
★ Proteome microarray
★ Infant
★ Serum

論文目次

摘要......................................................i
ABSTRACT................................................iii
誌謝......................................................v
Table of Contents........................................vi
List of Figures........................................viii
List of Tables............................................x
I INTRODUCTION............................................1
I. 1. Immune system.......................................1
I. 1. 1. Innate immune system.............................3
I. 1. 2. Adaptive immune system...........................3
I. 2. Immunoglobulin......................................4
I. 2. 1. Immunoglobulin A.................................6
I. 2. 2. Immunoglobulin G.................................6
I. 2. 3. Immunoglobulin M.................................7
I. 3. Commensal intestine bacteria and humoral immunity
maturation in infants...............................8
I. 4. Gene Ontology database..............................9
I. 5. Study hypothesis and goal..........................10
II MATERIALS AND METHODS.................................11
II. 1. Profiling comparison of infant and adult serum....11
II. 2. Cluster analysis..................................12
II. 2. 1. K-means clustering.............................13
II. 2. 1. 1. The K-means algorithm.......................13
II. 2. 2. Hierarchical clustering....................... 14
II. 2. 2. 1. Euclidean’s distance.......................15
II. 2. 2. 2. Complete linkage algorithm..................15
II. 3. BiNGO analysis....................................16
II. 3. 1. The hypergeometric distribution................16
II. 4. Significance analysis of E. coli proteome
microarrays.......................................17
III. RESULTS.............................................19
III. 1. Differentiate between infant and adult serum
samples..........................................19
III. 1. 1. List of lowly and highly immunogenic serum
samples.......................................20
III. 2. Identification of the proteins which induced the
samples to low or high immunogenicity............21
III. 2. 1. IgM profiling.................................21
III. 2. 2. IgG profiling.................................22
III. 2. 3. IgA profiling.................................23
III. 3. Statistically significant functionalities of
proteins which induced the samples to low or
high immunogenicity..............................24
III. 3. 1. IgM profiling.................................25
III. 3. 2. IgG profiling.................................27
III. 3. 3. IgA profiling.................................29
III. 3. 4. Common appearance in IgA, IgG and IgM
profiling.....................................31
III. 4. Significant variations of proteins among
2M_antibody, 12M_antibody and adult antibody
profiling proteome microarrays...................31
III. 4. 1. IgM profiling.................................32
III. 4. 2. IgG profiling.................................33
III. 4. 3. IgA profiling.................................34
III. 4. 4. Common appearance in IgA, IgG and IgM
profiling.....................................35
IV. DISCUSSION...........................................36
IV. 1. A rapid, reliable and high-throughput technology
to analyze infant and adult sera..................36
IV. 2. The mutual phenomena on each antibody profiling...37
IV. 3. Specific functionality in a specific antibody
profiling.........................................37
V. CONCLUSION............................................38
VI. REFERENCES...........................................39
FIGURES..................................................42
TABLES...................................................87

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指導教授

陳健生(Chien-Sheng Chen)

審核日期

2012-7-31

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