Asoke K. Nandi, Department of Electronic & Computer Engineering, Brunel University London, UKProf. Nandi is Chair and Head of the Electronic and Computer Engineering Department at Brunel University London, UK. He leads the Signal Processing and Communications Research Group with interests in the areas of signal processing, machine learning, and communications research. He is a Finland Distinguished Professor at the University of Jyvaskyla, Finland. In 1983 Professor Nandi was a member of the UA1 team at CERN that discovered the three fundamental particles known as W+, W- and Z0, providing the evidence for the unification of the electromagnetic and weak forces, which was recognized by the Nobel Committee for Physics in 1984. He has authored or co-authored more than 190 journal papers, and 2 books. The Google Scholar h-index of his publications is 54. In 2010 he received the Glory of Bengal Award for his outstanding achievements in scientific research, and in 2012 was awarded the IEEE Heinrich Hertz Award. Prof. Nandi is a Fellow of the IEEE.Rui Fa, Department of Electronic & Computer Engineering, Brunel University London, UKDr. Fa is a Senior Reseach Fellow in the Department of Electronic & Computer Engineering at Brunel University London, UK. Prior to this, he held research positions at the University of York and the University of Leeds working in radar signal processing and wireless communication projects. His current research interests include bioinformatics, machine learning, Bayesian statistics, statistical signal processing, and network science. Dr Rui Fa received his Bachelor and Master degrees in electronic and electrical engineering from Nanjing University of Science and Technology, China, in 2000 and in 2003, respectively, and his PhD degree in electrical engineering from University of Newcastle, UK, in 2007.Basel Abu-Jamous, Department of Electronic & Computer Engineering, Brunel University London, UKBasel Abu-Jamous is currently studying for his PhD in electrical engineering & electronics at Brunel University London, UK. His research interests include bioinformatics, computational biology, and the broader areas of information engineering and machine learning.Basel Abu-Jamous received his B.Sc. degree in computer engineering from the University of Jordan, Amman, Jordan, in 2010. He received his M.Sc. degree in information and intelligence engineering from the University of Liverpool, Liverpool, U.K., in 2011. He was awarded the Sir Robin Saxby Prize of the 2010/2011 academic year based on his performance in his M.Sc. degree.

• Preface xixList of Symbols xxiAbout the Authors xxiiiPart One Introduction 11 Introduction to Bioinformatics 32 Computational Methods in Bioinformatics 9Part Two Introduction to Molecular Biology 193 The Living Cell 214 Central Dogma of Molecular Biology 33Part Three Data Acquisition and Pre-processing 535 High-throughput Technologies 556 Databases, Standards and Annotation 677 Normalisation 878 Feature Selection 1099 Differential Expression 119Part Four Clustering Methods 13310 Clustering Forms 13511 Partitional Clustering 14312 Hierarchical Clustering 15713 Fuzzy Clustering 16714 Neural Network-based Clustering 18115 Mixture Model Clustering 19716 Graph Clustering 22717 Consensus Clustering 24718 Biclustering 26519 Clustering Methods Discussion 283Part Five Validation and Visualisation 30320 Numerical Validation 30521 Biological Validation 32322 Visualisations and Presentations 339Part Six New Clustering Frameworks Designed for Bioinformatics 36323 Splitting-Merging Awareness Tactics (SMART) 36524 Tightness-tunable Clustering (UNCLES) 385Appendix 395Index 409

Asoke K. Nandi, Department of Electronic & Computer Engineering, Brunel University London, UKProf. Nandi is Chair and Head of the Electronic and Computer Engineering Department at Brunel University London, UK. He leads the Signal Processing and Communications Research Group with interests in the areas of signal processing, machine learning, and communications research. He is a Finland Distinguished Professor at the University of Jyvaskyla, Finland. In 1983 Professor Nandi was a member of the UA1 team at CERN that discovered the three fundamental particles known as W+, W- and Z0, providing the evidence for the unification of the electromagnetic and weak forces, which was recognized by the Nobel Committee for Physics in 1984. He has authored or co-authored more than 190 journal papers, and 2 books. The Google Scholar h-index of his publications is 54. In 2010 he received the Glory of Bengal Award for his outstanding achievements in scientific research, and in 2012 was awarded the IEEE Heinrich Hertz Award. Prof. Nandi is a Fellow of the IEEE.Rui Fa, Department of Electronic & Computer Engineering, Brunel University London, UKDr. Fa is a Senior Reseach Fellow in the Department of Electronic & Computer Engineering at Brunel University London, UK. Prior to this, he held research positions at the University of York and the University of Leeds working in radar signal processing and wireless communication projects. His current research interests include bioinformatics, machine learning, Bayesian statistics, statistical signal processing, and network science. Dr Rui Fa received his Bachelor and Master degrees in electronic and electrical engineering from Nanjing University of Science and Technology, China, in 2000 and in 2003, respectively, and his PhD degree in electrical engineering from University of Newcastle, UK, in 2007.Basel Abu-Jamous, Department of Electronic & Computer Engineering, Brunel University London, UKBasel Abu-Jamous is currently studying for his PhD in electrical engineering & electronics at Brunel University London, UK. His research interests include bioinformatics, computational biology, and the broader areas of information engineering and machine learning.Basel Abu-Jamous received his B.Sc. degree in computer engineering from the University of Jordan, Amman, Jordan, in 2010. He received his M.Sc. degree in information and intelligence engineering from the University of Liverpool, Liverpool, U.K., in 2011. He was awarded the Sir Robin Saxby Prize of the 2010/2011 academic year based on his performance in his M.Sc. degree.

• Preface xixList of Symbols xxiAbout the Authors xxiiiPart One Introduction 11 Introduction to Bioinformatics 32 Computational Methods in Bioinformatics 9Part Two Introduction to Molecular Biology 193 The Living Cell 214 Central Dogma of Molecular Biology 33Part Three Data Acquisition and Pre-processing 535 High-throughput Technologies 556 Databases, Standards and Annotation 677 Normalisation 878 Feature Selection 1099 Differential Expression 119Part Four Clustering Methods 13310 Clustering Forms 13511 Partitional Clustering 14312 Hierarchical Clustering 15713 Fuzzy Clustering 16714 Neural Network-based Clustering 18115 Mixture Model Clustering 19716 Graph Clustering 22717 Consensus Clustering 24718 Biclustering 26519 Clustering Methods Discussion 283Part Five Validation and Visualisation 30320 Numerical Validation 30521 Biological Validation 32322 Visualisations and Presentations 339Part Six New Clustering Frameworks Designed for Bioinformatics 36323 Splitting-Merging Awareness Tactics (SMART) 36524 Tightness-tunable Clustering (UNCLES) 385Appendix 395Index 409

Asoke K. Nandi, Department of Electronic & Computer Engineering, Brunel University London, UKProf. Nandi is Chair and Head of the Electronic and Computer Engineering Department at Brunel University London, UK. He leads the Signal Processing and Communications Research Group with interests in the areas of signal processing, machine learning, and communications research. He is a Finland Distinguished Professor at the University of Jyvaskyla, Finland. In 1983 Professor Nandi was a member of the UA1 team at CERN that discovered the three fundamental particles known as W+, W- and Z0, providing the evidence for the unification of the electromagnetic and weak forces, which was recognized by the Nobel Committee for Physics in 1984. He has authored or co-authored more than 190 journal papers, and 2 books. The Google Scholar h-index of his publications is 54. In 2010 he received the Glory of Bengal Award for his outstanding achievements in scientific research, and in 2012 was awarded the IEEE Heinrich Hertz Award. Prof. Nandi is a Fellow of the IEEE.Rui Fa, Department of Electronic & Computer Engineering, Brunel University London, UKDr. Fa is a Senior Reseach Fellow in the Department of Electronic & Computer Engineering at Brunel University London, UK. Prior to this, he held research positions at the University of York and the University of Leeds working in radar signal processing and wireless communication projects. His current research interests include bioinformatics, machine learning, Bayesian statistics, statistical signal processing, and network science. Dr Rui Fa received his Bachelor and Master degrees in electronic and electrical engineering from Nanjing University of Science and Technology, China, in 2000 and in 2003, respectively, and his PhD degree in electrical engineering from University of Newcastle, UK, in 2007.Basel Abu-Jamous, Department of Electronic & Computer Engineering, Brunel University London, UKBasel Abu-Jamous is currently studying for his PhD in electrical engineering & electronics at Brunel University London, UK. His research interests include bioinformatics, computational biology, and the broader areas of information engineering and machine learning.Basel Abu-Jamous received his B.Sc. degree in computer engineering from the University of Jordan, Amman, Jordan, in 2010. He received his M.Sc. degree in information and intelligence engineering from the University of Liverpool, Liverpool, U.K., in 2011. He was awarded the Sir Robin Saxby Prize of the 2010/2011 academic year based on his performance in his M.Sc. degree.

• Preface xixList of Symbols xxiAbout the Authors xxiiiPart One Introduction 11 Introduction to Bioinformatics 32 Computational Methods in Bioinformatics 9Part Two Introduction to Molecular Biology 193 The Living Cell 214 Central Dogma of Molecular Biology 33Part Three Data Acquisition and Pre-processing 535 High-throughput Technologies 556 Databases, Standards and Annotation 677 Normalisation 878 Feature Selection 1099 Differential Expression 119Part Four Clustering Methods 13310 Clustering Forms 13511 Partitional Clustering 14312 Hierarchical Clustering 15713 Fuzzy Clustering 16714 Neural Network-based Clustering 18115 Mixture Model Clustering 19716 Graph Clustering 22717 Consensus Clustering 24718 Biclustering 26519 Clustering Methods Discussion 283Part Five Validation and Visualisation 30320 Numerical Validation 30521 Biological Validation 32322 Visualisations and Presentations 339Part Six New Clustering Frameworks Designed for Bioinformatics 36323 Splitting-Merging Awareness Tactics (SMART) 36524 Tightness-tunable Clustering (UNCLES) 385Appendix 395Index 409