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Computing Genomic Science: Bioinformatics and Standardisation in Proteomics Computing Genomic Science: Bioinformatics and Standardisation in Proteomics by Jamie Lewis Cardiff University This thesis is submitted to the University of Wales in fulfilment of the requirements for the degree of DOCTOR IN PHILOSOPHY UMI Number: U585242 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U585242 Published by ProQuest LLC 2013. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Declaration This work has not previously been accepted in substance for any degree and is not concurrently submitted in candidature for any degree. Signed:.. (candidate) Date:....................................................... STATEMENT 1 This thesis is being submitted in partial fulfilment of the requirements for the degree of PhD. Signed ...................... (candidate) Date:....... ................................................ STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated. Other sources are acknowledged by explicit references. A bibliography is appended. Signed.. A . Q w y l (candidate) Date:....... ................................................ STATEMENT 3 I hereby give my consent for my thesis, if accepted, to be available for photocopying and for the inter-library loan, and for the title and summary to be made available to outside organisations. Signed f.i................... (candidate) Date:........'X& ........................ Acknowledgments Unfortunately I have a limited word count so I cannot thank everyone I would like to. However, there are several people without whose time, support, generosity and faith I would not have reached this point. First, I am greatly indebted to Sara Delamont and Paul Atkinson without whom I would never have done a Ph.D. They have been a source of great inspiration to me. Special thanks are also reserved for Beck, Pam and Helen G for spending hours checking my references and proof reading, and Andy, Ingrid and Neil for their invaluable academic input. They, together with Alex, Amy, Cathy, Helen B, Jackie, Jasmin, Jo, Kelly, Liz, Maggie, Mark, Martin, Mel, Nina and Oily have been a source of support, friendship, motivation and help. I would also like to thank my supervisors Peter and Ruth, my examiners Nik and Steve, and the KES group for their critique and comments. Thanks must also be reserved for the ESRC for their appreciated financial contribution and Cesagen members for their kindness and encouragement. Last but certainly not least, I would like to thank my family for their love and support. I particularly would like to dedicate this thesis to my Mum and Dad who have always encouraged me to pursue my own career and have supported me through a few health problems. Efallai nad yw hwn o safon Da Vinci, ond fe wnes ify ngorau glas! Summary Science is divided and compartmentalised into distinct areas of research. As science develops new research areas emerge and nurture new technologies, new methodological approaches, new disciplines and new research communities. These demarcations are socially constructed spaces that impose a sense of order on science by authenticating the new forms of knowledge that surface. Simply stated, the specific research areas and the social relations contained within them, enable science to progress in a proficient, communal, and sometimes cumulative manner. In this sense the constructedboundaries can be viewed as a set of ordering devices. The mapping of the Human Genome was a significant technical event that reordered biological activity by creating a number of these new socially constructed spaces. This celebrated scientific achievement helped yield a number of emerging ‘omic’ disciplines, numerous innovative high-throughput technologies, and a myriad of embryonic scientific communities, each with its own distinct identity. In this thesis the Human Genome Project is viewed as the genomic stage of the omic revolution or stage one. The period directly after the sequencing has been coined the post-genomic era and this is described in the thesis as stage two of the social reorganisation of biology. Underpinning the whole thesis is the understanding that omic science is driven by a systems biology (SB) approach to twenty-first century biology. The realisation of this will constitute stage three. Computational biologists are also using a similar model of scientific practice in order to map, trace and direct future scientific practice. However in using this developmental model, the organisation of scientific practice may turn messy when boundaries need to be permeated, re-aligned and re-ordered in the movement from post-genomic science to systems biology science. Consequently the specific aim of this research is to trace how two of these maturing research areas,proteomics' ‘ and ‘ bioinformatics ’, are emerging and stabilising within stage two of the omic model, and to explore some of the social issues that are being reordered within their infrastructure. Drawing upon thirty-one interviews the research provides valuable insight into the social construction of post-genomic knowledge and adds to the growing literature in the field ofscience and technology studies (STS) by revealing how socially constructed knowledges are translated and transferred within and between newly created scientific communities. This is achieved through an examination of scientific identity, interdisciplinary expertise and community-based standardisation. Table of Contents Declaration i Acknowledgements ii Summary iii Table of Contents iv List of Figures ix List of Tables ix Chapter One: Studying Science — Science and Technology Studies (STS) 1 Prologue 1 Introduction 2 Sensational Science 2 Sensing Science 5 Thesis Themes and Questions 8 Why Study Science? New Biology’s Impact on Society in the UK 10 How to Study Science: Science Communities and Scientific Practice 11 Thesis Synopsis 13 Chapter Two: Proteomics and Bioinformatics: A Social Scientist’s Primer 17 Part One - Proteomics Introduction 17 What are Proteins? 18 Complex and Convoluted Chains 20 What is a Proteome? From Proteins to the Proteome 21 Proteomics: A Succinct Definition and History 22 Electrophoresis, Mass Spectrometry and Proteomics 23 The Human Protein Index (HPI) 25 Big Science Projects: from Reductionism to Holism 26 The Beginnings of Systems Biology 27 Preparing for the Human Genome Project 28 The Human Genome Project and the Human Genome Organisation 29 From the Proto-omic to Proteomics 32 Genome to Proteome: A Problem and a Promise 33 The Development of the Human Proteome Organisation 34 What has HUPO and Proteomics Achieved? The Story so Far 36 Part Two - Bioinformatics Introduction 38 The Beginnings of Bioinformatics: A Short History 40 Bioinformatics Software Programmes 44 The European Bioinformatics Institute 45 The Proteomics Standards Initiative 47 Summary 48 Chapter Three: Standards, Boundary Classifications and Paradigm Shifts 50 Introduction 50 The Beginnings of Method as a Standard 51 Law and Order: The Necessity of Method 54 Classifications and their Consequences: Three Accounts of Standardisation 56 Standards and Classification as a Process: The Birth of STS 64 Science Segregation and Boundary Classification 68 A Short Account of Standardisation in Proteomics 72 Conclusion 74 Chapter Four: Methodological Reflections: A Social Scientist in a Natural Scientists’ Setting 77 Introduction 77 Qualitative Research and Social Constructionism 78 Types of Methods 80 Negotiating Access and Gatekeepers 81 Sampling - Who to Study? 84 Ethical Issues 86 Site Visit/Observation (Stage One) 87 v Semi-Structured Interviews: The Structure and the Setting (Stage Two) 90 RSDDP Protein Bioinformatics Course (Stage Three) 93 Email 95 Elite Interviewing 95 Action Research 98 Interactional Expertise: The Sociologist of Science 102 Analysis 105 Conclusion 107 Chapter Five: Beyond Boundaries: Performing the Promise of Proteomics 110 Introduction 110 Organising Knowledge: Construction of Boundaries within Scientific Practice 112 The Boundary Object 118 Placing Proteomics: What is it? 120 From Buzz-Word to Boundary Object: The Promise of Proteomics 127 Rhetorical Tactics to Gain Funding 133 Proto-Boundary and Proto-Proteomics: The Importance of Funding in Science 135 Conclusion: The Real Consequences of the Imagined Boundary 140 Chapter Six: Scripting the Gold-Standard: Whose Standard is it Anyway? 145 Introduction 145 Why Study Standards? 147 What do Standards do? 149 Scripting Imagined Biological Futures 153 From a Science Model to a Social Pathway: A Particular Focus on the Standardisation Process 160 Competing Standards 173 Conclusion 176 Chapter Seven: Computing Biological Identities 179 Introduction 179 Bioinformatics and Systems Biology 181 Locating Bioinformatics 183 vi Division of Labour and the Demiurge: The Craftsman or the Computer Machine 186 Bioinformaticists and Bioinformaticians 194 The Proteomics Facility 198 Conclusion 200 Chapter Eight: Matchmakers and Speed-Daters: Cross-Collaborative Arrangements in Bioinformatics and Proteomics
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