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vi Editors in Chief

Christian Schö nbach is currently Department Chair and Professor at Department of Biology,
School of Science and Technology, Nazarbayev University, Kazakhstan and Visiting Professor at
International Research Center for Medical Sciences at Kumamoto University, Japan. He is a
bioinformatics practitioner interfacing genetics, immunology and informatics conducting
research on major histocompatibility complex, immune responses following virus infection,
biomedical knowledge discovery, peroxisomal diseases, and autism spectrum disorder that
resulted in more than 80 publications. His previous academic appointments included Pro-
fessor at Kumamoto University (2016–2017), Nazarbayev University (2013–2016), Kazakh-
stan, Kyushu Institute of Technology (2009–2013) Japan, Associate Professor at Nanyang
Technological University (2006–2009), Singapore, and Team Leader at RIKEN Genomic Sci-
ences Center (2002–2006), Japan. Other prior positions included Principal Investigator at Kent
Ridge Digital Labs, Singapore and Research Scientist at Chugai Institute for Molecular Medi-
cine, Inc., Japan. In 2018 he became a member of International Society for Computational Biology (ISCB) Board of Directors.
Since 2010 he is serving Asia-Pacific Bioinformatics Network (APBioNet) as Vice-President (Conferences 2010–2016) and Pre-
sident (2016–2018).
VOLUME EDITORS

Mario Cannataro is a Full Professor of Computer Engineering and Bioinformatics at Uni-

versity “Magna Graecia” of Catanzaro, Italy. He is the director of the Data Analytics research
center and the chair of the Bioinformatics Laboratory at University “Magna Graecia” of
Catanzaro. His current research interests include bioinformatics, medical informatics, data
analytics, parallel and distributed computing. He is a Member of the editorial boards of
Briefings in Bioinformatics, High-Throughput, Encyclopedia of Bioinformatics and Compu-
tational Biology, Encyclopedia of Systems Biology. He was guest editor of several special
issues on bioinformatics and he is serving as a program committee member of several con-
ferences. He published three books and more than 200 papers in international journals and
conference proceedings. Prof. Cannataro is a Senior Member of IEEE, ACM and BITS, and a
member of the Board of Directors for ACM SIGBIO.

Bruno Gaeta is Senior Lecturer and Director of Studies in Bioinformatics in the School of
Computer Science and Engineering at UNSW Australia. His research interests cover multiple
areas of bioinformatics including gene regulation and protein structure, currently with a focus
on the immune system, antibody genes and the generation of antibody diversity. He is a
pioneer of bioinformatics education and has trained thousands of biologists and trainee
bioinformaticians in the use of computational tools for biological research through courses,
workshops as well as a book series. He has worked both in academia and in the bioinfor-
matics industry, and currently coordinates the largest bioinformatics undergraduate program
in Australia.

Mohammad Asif Khan, PhD, is an associate professor and the Dean of the School of Data
Sciences, as well as the Director of the Centre for Bioinformatics at Perdana University,
Malaysia. He is also a visiting scientist at the Department of Pharmacology and Molecular
Sciences, Johns Hopkins University School of Medicine (JHUSOM), USA. His research
interests are in the area of biological data warehousing and applications of bioinformatics to
the study of immune responses, vaccines, inhibitory drugs, venom toxins, and disease bio-
markers. He has published in these areas, been involved in the development of several novel
bioinformatics methodologies, tools, and specialized databases, and currently has three
patent applications granted. He has also led the curriculum development of a Postgraduate
Diploma in Bioinformatics programme and an MSc (Bioinformatics) programme at Perdana
University. He is an elected ExCo member of the Asia-Pacific Bioinformatics Network
(APBioNET) since 2010 and is currently the President of Association for Medical and Bio-
Informatics, Singapore (AMBIS). He has donned various important roles in the organization
of many local and international bioinformatics conferences, meetings and workshops.

vii
CONTENTS OF VOLUME 1

Editors in Chief v
Volume Editors vii
List of Contributors for Volume 1 xvii
Preface xxi

VOLUME 1

Algorithms Foundations
Nadia Pisanti 1
Techniques for Designing Bioinformatics Algorithms
Massimo Cafaro, Italo Epicoco, and Marco Pulimeno 5
Algorithms for Strings and Sequences: Searching Motifs
Francesco Cauteruccio, Giorgio Terracina, and Domenico Ursino 15
Algorithms for Strings and Sequences: Pairwise Alignment
Stefano Beretta 22
Algorithms for Strings and Sequences: Multiple Alignment
Pietro H Guzzi 30
Algorithms for Structure Comparison and Analysis: Prediction of Tertiary Structures of Proteins
Giuseppe Tradigo, Francesca Rondinelli, and Gianluca Pollastri 32
Algorithms for Structure Comparison and Analysis: Homology Modelling of Proteins
Marco Wiltgen 38
Ab initio Protein Structure Prediction
Rahul Kaushik, Ankita Singh, and B Jayaram 62
Algorithms for Structure Comparison and Analysis: Docking
Giuseppe Tradigo, Francesca Rondinelli, and Gianluca Pollastri 77
Algorithms for Graph and Network Analysis: Graph Indexes/Descriptors
Lo Giudice Paolo and Domenico Ursino 81
Algorithms for Graph and Network Analysis: Traversing/Searching/Sampling Graphs
Paolo Lo Giudice and Domenico Ursino 89
Algorithms for Graph and Network Analysis: Clustering and Search of Motifs in Graphs
Clara Pizzuti and Simona E Rombo 95
Algorithms for Graph and Network Analysis: Graph Alignment
Luigi Palopoli and Simona E Rombo 102
Bioinformatics Data Models, Representation and Storage
Mariaconcetta Bilotta, Giuseppe Tradigo, and Pierangelo Veltri 110
Data Storage and Representation
Antonella Guzzo 117
Experimental Platforms for Extracting Biological Data: Mass Spectrometry, Microarray, Next
Generation Sequencing
Barbara Calabrese 126

ix
x Contents of Volume 1

Standards and Models for Biological Data: Common Formats

Barbara Calabrese 130
Standards and Models for Biological Data: FGED and HUPO
Barbara Calabrese 137
Standards and Models for Biological Data: SBML
Giuseppe Agapito 142
Standards and Models for Biological Data: BioPAX
Giuseppe Agapito 147
Models for Computable Phenotyping
Alfredo Tirado-Ramos and Laura Manuel 154
Computing for Bioinformatics
Mario Cannataro and Giuseppe Agapito 160
Computing Languages for Bioinformatics: Perl
Giuseppe Agapito 176
Computing Languages for Bioinformatics: BioPerl
Giuseppe Agapitoa 187
Computing Languages for Bioinformatics: Python
Pietro H Guzzi 195
Computing Languages for Bioinformatics: R
Marianna Milano 199
Computing Languages for Bioinformatics: Java
Pietro H Guzzi 206
Parallel Architectures for Bioinformatics
Ivan Merelli 209
Models and Languages for High-Performance Computing
Domenico Talia 215
MapReduce in Computational Biology Via Hadoop and Spark
Giuseppe Cattaneo, Raffaele Giancarlo, Umberto Ferraro Petrillo, and Gianluca Roscigno 221
Infrastructure for High-Performance Computing: Grids and Grid Computing
Ivan Merelli 230
Infrastructures for High-Performance Computing: Cloud Computing
Paolo Trunfio 236
Infrastructures for High-Performance Computing: Cloud Infrastructures
Fabrizio Marozzo 240
Infrastructures for High-Performance Computing: Cloud Computing Development
Environments
Fabrizio Marozzo and Paolo Trunfio 247
Cloud-Based Bioinformatics Tools
Barbara Calabrese 252
Cloud-Based Bioinformatics Platforms
Barbara Calabrese 257
Cloud-Based Molecular Modeling Systems
Barbara Calabrese 261
The Challenge of Privacy in the Cloud
Francesco Buccafurri, Vincenzo De Angelis, Gianluca Lax, Serena Nicolazzo, and Antonino Nocera 265
 Contents of Volume 1 xi

Artificial Intelligence and Machine Learning in Bioinformatics

Kaitao Lai, Natalie Twine, Aidan O’Brien, Yi Guo, and Denis Bauer 272
Artificial Intelligence
Francesco Scarcello 287
Knowledge and Reasoning
Francesco Ricca and Giorgio Terracina 294
Machine Learning in Bioinformatics
Jyotsna T Wassan, Haiying Wang, and Huiru Zheng 300
Intelligent Agents and Environment
Alfredo Garro, Max Mühlhäuser, Andrea Tundis, Stefano Mariani, Andrea Omicini, and Giuseppe Vizzari 309
Intelligent Agents: Multi-Agent Systems
Alfredo Garro, Max Mühlhäuser, Andrea Tundis, Matteo Baldoni, Cristina Baroglio, Federico Bergenti, and
Paolo Torroni 315
Stochastic Methods for Global Optimization and Problem Solving
Giovanni Stracquadanio and Panos M Pardalos 321
Data Mining in Bioinformatics
Chiara Zucco 328
Knowledge Discovery in Databases
Massimo Guarascio, Giuseppe Manco, and Ettore Ritacco 336
Supervised Learning: Classification
Mauro Castelli, Leonardo Vanneschi, and Álvaro Rubio Largo 342
Unsupervised Learning: Clustering
Angela Serra and Roberto Tagliaferri 350
Data Mining: Mining Frequent Patterns, Associations Rules, and Correlations
Massimo Cafaro, Italo Epicoco, and Marco Pulimeno 358
Association Rules and Frequent Patterns
Giuseppe Di Fatta 367
Decision Trees and Random Forests
Michele Fratello and Roberto Tagliaferri 374
Data Mining: Classification and Prediction
Alfonso Urso, Antonino Fiannaca, Massimo La Rosa, Valentina Ravì, and Riccardo Rizzo 384
Bayes’ Theorem and Naive Bayes Classifier
Daniel Berrar 403
Data Mining: Prediction Methods
Alfonso Urso, Antonino Fiannaca, Massimo La Rosa, Valentina Ravì, and Riccardo Rizzo 413
Data Mining: Accuracy and Error Measures for Classification and Prediction
Paola Galdi and Roberto Tagliaferri 431
Data Mining: Clustering
Alessia Amelio and Andrea Tagarelli 437
Computation Cluster Validation in the Big Data Era
Raffaele Giancarlo and Filippo Utro 449
Data Mining: Outlier Detection
Fabrizio Angiulli 456
xii Contents of Volume 1

Pre-Processing: A Data Preparation Step

Swarup Roy, Pooja Sharma, Keshab Nath,
Dhruba K Bhattacharyya, and Jugal K Kalita 463
Data Cleaning
Barbara Calabrese 472
Data Integration and Transformation
Barbara Calabrese 477
Data Reduction
Barbara Calabrese 480
Dimensionality Reduction
Italia De Feis 486
Kernel Machines: Introduction
Italo Zoppis, Giancarlo Mauri, and Riccardo Dondi 495
Kernel Methods: Support Vector Machines
Italo Zoppis, Giancarlo Mauri, and Riccardo Dondi 503
Kernel Machines: Applications
Italo Zoppis, Giancarlo Mauri, and Riccardo Dondi 511
Multiple Learners Combination: Introduction
Chiara Zucco 519
Multiple Learners Combination: Bagging
Chiara Zucco 525
Multiple Learners Combination: Boosting
Chiara Zucco 531
Multiple Learners Combination: Stacking
Chiara Zucco 536
Multiple Learners Combination: Cascading
Chiara Zucco 539
Cross-Validation
Daniel Berrar 542
Performance Measures for Binary Classification
Daniel Berrar 546
Natural Language Processing Approaches in Bioinformatics
Xu Han and Chee K Kwoh 561
Text Mining Basics in Bioinformatics
Carmen De Maio, Giuseppe Fenza, Vincenzo Loia, and Mimmo Parente 575
Data-Information-Concept Continuum From a Text Mining Perspective
Danilo Cavaliere, Sabrina Senatore, and Vincenzo Loia 586
Text Mining for Bioinformatics Using Biomedical Literature
Andre Lamurias and Francisco M Couto 602
Multilayer Perceptrons
Leonardo Vanneschi and Mauro Castelli 612
Delta Rule and Backpropagation
Leonardo Vanneschi and Mauro Castelli 621
Deep Learning
Massimo Guarascio, Giuseppe Manco, and Ettore Ritacco 634
 Contents of Volume 1 xiii

Introduction to Biostatistics
Antonella Iuliano and Monica Franzese 648
Descriptive Statistics
Monica Franzese and Antonella Iuliano 672
Measurements of Accuracy in Biostatistics
Haiying Wang, Jyotsna T Wassan, and Huiru Zheng 685
Hypothesis Testing
Claudia Angelini 691
Statistical Inference Techniques
Daniela De Canditiis 698
Correlation Analysis
Monica Franzese and Antonella Iuliano 706
Regression Analysis
Claudia Angelini 722
Nonlinear Regression Models
Audrone Jakaitiene 731
Parametric and Multivariate Methods
Luisa Cutillo 738
Stochastic Processes
Maria Francesca Carfora 747
Hidden Markov Models
Monica Franzese and Antonella Iuliano 753
Linkage Disequilibrium
Barbara Calabrese 763
Introduction to the Non-Parametric Bootstrap
Daniel Berrar 766
Population-Based Sampling and Fragment-Based De Novo Protein Structure Prediction
David Simoncini and Kam YJ Zhang 774
Ontology: Introduction
Gianluigi Greco, Marco Manna, and Francesco Ricca 785
Ontology: Definition Languages
Valeria Fionda and Giuseppe Pirrò 790
Ontology: Querying Languages and Development
Valeria Fionda and Giuseppe Pirrò 800
Ontology in Bioinformatics
Pietro Hiram Guzzi 809
Biological and Medical Ontologies: Introduction
Marco Masseroli 813
Biological and Medical Ontologies: GO and GOA
Marco Masseroli 823
Biological and Medical Ontologies: Protein Ontology (PRO)
Davide Chicco and Marco Masseroli 832
Biological and Medical Ontologies: Disease Ontology (DO)
Anna Bernasconi and Marco Masseroli 838
xiv Contents of Volume 1

Biological and Medical Ontologies: Human Phenotype Ontology (HPO)

Anna Bernasconi and Marco Masseroli 848
Biological and Medical Ontologies: Systems Biology Ontology (SBO)
Anna Bernasconi and Marco Masseroli 858
Ontology-Based Annotation Methods
Pietro H Guzzi 867
Semantic Similarity Definition
Francisco M Couto and Andre Lamurias 870
Semantic Similarity Functions and Measures
Giuseppe Pirrò 877
Tools for Semantic Analysis Based on Semantic Similarity
Marianna Milano 889
Functional Enrichment Analysis Methods
Pietro H Guzzi 896
Gene Prioritization Using Semantic Similarity
Erinija Pranckeviciene 898
Gene Prioritization Tools
Marianna Milano 907
Networks in Biology
Valeria Fionda 915
Graph Theory and Definitions
Stefano Beretta, Luca Denti, and Marco Previtali 922
Network Properties
Stefano Beretta, Luca Denti, and Marco Previtali 928
Graph Isomorphism
Riccardo Dondi, Giancarlo Mauri, and Italo Zoppis 933
Graph Algorithms
Riccardo Dondi, Giancarlo Mauri, and Italo Zoppis 940
Network Centralities and Node Ranking
Raffaele Giancarlo, Daniele Greco, Francesco Landolina, and Simona E Rombo 950
Network Topology
Giuseppe Manco, Ettore Ritacco, and Massimo Guarascio 958
Network Models
Massimo Guarascio, Giuseppe Manco, and Ettore Ritacco 968
Community Detection in Biological Networks
Marco Pellegrini 978
Protein–Protein Interaction Databases
Max Kotlyar, Chiara Pastrello, Andrea EM Rossos, and Igor Jurisica 988
Alignment of Protein-Protein Interaction Networks
Swarup Roy, Hazel N Manners, Ahed Elmsallati, and Jugal K Kalita 997
Visualization of Biomedical Networks
Anne-Christin Hauschild, Chiara Pastrello, Andrea EM Rossos, and Igor Jurisica 1016
Cluster Analysis of Biological Networks
Asuda Sharma, Hesham Ali, and Dario Ghersi 1036
 Contents of Volume 1 xv

Biological Pathways
Giuseppe Agapito 1047
Biological Pathway Data Formats and Standards
Ramakanth C Venkata and Dario Ghersi 1063
Biological Pathway Analysis
Ramakanth Chirravuri Venkata and Dario Ghersi 1067
Two Decades of Biological Pathway Databases: Results and Challenges
Sara Rahmati, Chiara Pastrello, Andrea EM Rossos, and Igor Jurisica 1071
Visualization of Biological Pathways
Giuseppe Agapito 1085
Integrative Bioinformatics
Marco Masseroli 1092
Integrative Bioinformatics of Transcriptome: Databases, Tools and Pipelines
Maria T Di Martino and Pietro H Guzzi 1099
Information Retrieval in Life Sciences
Pietro Cinaglia, Domenico Mirarchi, and Pierangelo Veltri 1104
LIST OF CONTRIBUTORS FOR VOLUME 1

Giuseppe Agapito Mario Cannataro

University “Magna Graecia” of Catanzaro, University “Magna Graecia” of Catanzaro, Catanzaro,
Catanzaro, Italy Italy

Hesham Ali Maria Francesca Carfora

University of Nebraska at Omaha, Omaha, NE, Istituto per le Applicazioni del Calcolo CNR, Napoli,
United States Italy

Alessia Amelio Mauro Castelli

University of Calabria, Rende, Italy NOVA IMS, Universidade Nova de Lisboa, Lisboa,
Portugal
Claudia Angelini
Giuseppe Cattaneo
Istituto per le Applicazioni del Calcolo “M. Picone”,
University of Salerno, Fisciano, Italy
Napoli, Italy
Francesco Cauteruccio
Fabrizio Angiulli University of Calabria, Rende, Italy
University of Calabria, Rende, Italy
Danilo Cavaliere
Matteo Baldoni Università degli Studi di Salerno, Fisciano, Italy
University of Turin, Turin, Italy
Davide Chicco
Cristina Baroglio Princess Margaret Cancer Centre, Toronto, ON, Canada
University of Turin, Turin, Italy Pietro Cinaglia
Denis Bauer Magna Graecia University of Catanzaro, Catanzaro,
CSIRO, North Ryde, NSW, Australia Italy
Francisco M. Couto
Stefano Beretta
Universidade de Lisboa, Lisboa, Portugal
University of Milan-Biocca, Milan, Italy
Luisa Cutillo
Federico Bergenti University of Sheffield, Sheffield, United Kingdom; and
University of Parma, Parma, Italy Parthenope University of Naples, Naples, Italy
Anna Bernasconi Vincenzo De Angelis
Politecnico di Milano, Milan, Italy University of Reggio Calabria, Italy
Daniel Berrar Daniela De Canditiis
Tokyo Institute of Technology, Tokyo, Japan Istituto per le Applicazioni del Calcolo “M. Picone”,
Rome, Italy
Dhruba K. Bhattacharyya
Tezpur University, Tezpur, India Italia De Feis
Istituto per le Applicazioni del Calcolo CNR, Napoli,
Mariaconcetta Bilotta Italy
University of Catanzaro, Catanzaro, Italy; and Institute
Carmen De Maio
S. Anna of Crotone, Crotone, Italy
University of Salerno, Fisciano, Italy
Francesco Buccafurri Luca Denti
University of Reggio Calabria, Italy University of Milan-Biocca, Milan, Italy
Massimo Cafaro Giuseppe Di Fatta
University of Salento, Lecce, Italy University of Reading, Reading, United Kingdom
Barbara Calabrese Maria T. Di Martino
University “Magna Graecia” of Catanzaro, University “Magna Graecia” of Catanzaro, Catanzaro,
Catanzaro, Italy Italy

xvii
xviii List of Contributors for Volume 1

Riccardo Dondi Antonella Iuliano

University of Bergamo, Bergamo, Italy Institute for Applied Mathematics “Mauro Picone”,
Napoli, Italy
Ahed Elmsallati
McKendree University, Lebanon, IL, United States Audrone Jakaitiene
Vilnius University, Vilnius, Lithuania
Italo Epicoco
University of Salento, Lecce, Italy B. Jayaram
IIT Delhi, New Delhi, India
Giuseppe Fenza
University of Salerno, Fisciano, Italy Igor Jurisica
University of Toronto, ON, Canada; and Slovak
Antonino Fiannaca Academy of Sciences, Bratislava, Slovakia
Via Ugo La Malfa, Palermo, Italy
Jugal K. Kalita
Valeria Fionda University of Colorado, Boulder, CO, United States
University of Calabria, Rende, Italy
Rahul Kaushik
Monica Franzese IIT Delhi, New Delhi, India
Institute for Applied Mathematics “Mauro Picone”, Max Kotlyar
Napoli, Italy University Health Network, Toronto, ON, Canada
Michele Fratello Chee K. Kwoh
DP Control, Salerno, Italy Nanyang Technological University, Singapore
Paola Galdi Massimo La Rosa
University of Salerno, Fisciano, Italy Via Ugo La Malfa, Palermo, Italy
Alfredo Garro Kaitao Lai
University of Calabria, Rende, Italy CSIRO, North Ryde, NSW, Australia
Dario Ghersi Andre Lamurias
University of Nebraska at Omaha, Omaha, NE, Universidade de Lisboa, Lisboa, Portugal
United States
Francesco Landolina
Raffaele Giancarlo University of Palermo, Palermo, Italy
University of Palermo, Palermo, Italy Álvaro Rubio Largo
Gianluigi Greco NOVA IMS, Universidade Nova de Lisboa, Lisboa,
University of Calabria, Cosenza, Italy Portugal

Daniele Greco Gianluca Lax

University of Palermo, Palermo, Italy University of Reggio Calabria, Italy
Paolo Lo Giudice
Massimo Guarascio
University “Mediterranea” of Reggio Calabria, Reggio
ICAR-CNR, Rende, Italy
Calabria, Italy
Yi Guo
Vincenzo Loia
Western Sydney University, Penrith, NSW, Australia
University of Salerno, Fisciano, Italy
Pietro H. Guzzi Max Mühlhäuser
University “Magna Graecia” of Catanzaro, Darmstadt University of Technology, Darmstadt,
Catanzaro, Italy Germany
Antonella Guzzo Giuseppe Manco
University of Calabria, Rende, Italy ICAR-CNR, Rende, Italy
Xu Han Marco Manna
Nanyang Technological University, Singapore University of Calabria, Cosenza, Italy
Anne-Christin Hauschild Hazel N. Manners
Krembil Research Institute, Toronto, ON, Canada North-Eastern Hill University, Shillong, India
 List of Contributors for Volume 1 xix

Laura Manuel Nadia Pisanti

University of Texas Health at San Antonio, San University of Pisa, Pisa, Italy
Antonio, TX, United States
Clara Pizzuti
Stefano Mariani Institute for High Performance Computing and
University of Bologna, Bologna, Italy Networking (ICAR), Cosenza, Italy
Fabrizio Marozzo Gianluca Pollastri
University of Calabria, Rende, Italy University College Dublin, Dublin, Ireland
Marco Masseroli Erinija Pranckeviciene
Polytechnic University of Milan, Milan, Italy Vilnius University, Vilnius, Lithuania
Giancarlo Mauri Marco Previtali
University of Milan-Biocca, Milan, Italy University of Milan-Biocca, Milan, Italy
Ivan Merelli Marco Pulimeno
Institute for Biomedical Technologies (CNR), Milan, University of Salento, Lecce, Italy
Italy; and National Research Council, Segrate, Italy
Sara Rahmati
Marianna Milano University of Toronto, Toronto, ON, Canada; and
University of Catanzaro, Catanzaro, Italy Krembil Research Institute, Toronto, ON, Canada
Domenico Mirarchi Valentina Ravì
Magna Graecia University of Catanzaro, Via Ugo La Malfa, Palermo, Italy
Catanzaro, Italy
Francesco Ricca
Keshab Nath University of Calabria, Rende, Italy
North-Eastern Hill University, Shillong, India
Ettore Ritacco
Serena Nicolazzo ICAR-CNR, Rende, Italy
University of Reggio Calabria, Italy
Riccardo Rizzo
Antonino Nocera ICAR-CNR, Rende, Italy
University of Reggio Calabria, Italy
Simona E. Rombo
Aidan O’Brien University of Palermo, Palermo, Italy
CSIRO, North Ryde, NSW, Australia
Francesca Rondinelli
Andrea Omicini Università degli Studi di Napoli Federico II, Napoli,
University of Bologna, Bologna, Italy Italy
Luigi Palopoli Gianluca Roscigno
Università della Calabria, Cosenza, Italy University of Salerno, Fisciano, Italy
Panos M.. Pardalos Andrea E.M. Rossos
University of Florida, Gainesville, FL, United States Krembil Research Institute, Toronto, ON, Canada
Mimmo Parente Swarup Roy
University of Salerno, Fisciano, Italy Sikkim University, Gangtok, India; and North-Eastern
Hill University, Shillong, India
Chiara Pastrello
Krembil Research Institute, Toronto, ON, Canada Francesco Scarcello
University of Calabria, Rende, Italy
Marco Pellegrini
Consiglio Nazionale delle Ricerche, Istituto di Sabrina Senatore
Informatica e Telematica, Pisa, Italy Università degli Studi di Salerno, Fisciano, Italy
Umberto Ferraro Petrillo Angela Serra
University of Rome “Sapienza”, Rome, Italy University of Salerno, Salerno, Italy
Giuseppe Pirrò Pooja Sharma
ICAR-CNR, Rende, Italy Tezpur University, Tezpur, India
xx List of Contributors for Volume 1

Asuda Sharma Alfonso Urso

University of Nebraska at Omaha, Omaha, NE, Via Ugo La Malfa, Palermo, Italy
United States
Filippo Utro
David Simoncini IBM Thomas J. Watson Research Center, Yorktown
University of Toulouse, Toulouse, France; and Heights, NY, United States
RIKEN, Yokohama, Japan
Leonardo Vanneschi
Ankita Singh
NOVA IMS, Universidade Nova de Lisboa, Lisboa,
IIT Delhi, New Delhi, India; and Banasthali
Portugal
Vidyapith, Banasthali, India
Giovanni Stracquadanio Pierangelo Veltri
University of Essex, Colchester, United Kingdom University “Magna Graecia” of Catanzaro, Catanzaro,
Italy
Andrea Tagarelli
University of Calabria, Rende, Italy Ramakanth C. Venkata
University of Nebraska at Omaha, Omaha, NE, United
Roberto Tagliaferri
States
University of Salerno, Salerno, Italy
Domenico Talia Giuseppe Vizzari
University of Calabria, Rende, Italy University of Milano-Bicocca, Milan, Italy

Giorgio Terracina Haiying Wang

University of Calabria, Rende, Italy Ulster University, Newtonabbey, Northern Ireland,
United Kingdom
Alfredo Tirado-Ramos
University of Texas Health at San Antonio, San Jyotsna T. Wassan
Antonio, TX, United States Ulster University, Newtonabbey, Northern Ireland,
Paolo Torroni United Kingdom
University of Bologna, Bologna, Italy
Marco Wiltgen
Giuseppe Tradigo Graz General Hospital and University Clinics, Graz,
University of Calabria, Rende, Italy; and University Austria
of Florida, Gainsville, United States
Kam Y.J. Zhang
Paolo Trunfio RIKEN, Yokohama, Japan
University of Calabria, Rende, Italy
Huiru Zheng
Andrea Tundis
Ulster University, Newtonabbey, Northern Ireland,
Darmstadt University of Technology, Darmstadt,
United Kingdom
Germany
Natalie Twine Italo Zoppis
CSIRO, North Ryde, NSW, Australia University of Milan-Biocca, Milan, Italy

Domenico Ursino Chiara Zucco

University “Mediterranea” of Reggio Calabria, Reggio University “Magna Graecia” of Catanzaro, Catanzaro,
Calabria, Italy Italy
PREFACE
Bioinformatics and Computational Biology (BCB) combine elements of computer science, information technology, mathematics,
statistics, and biotechnology, providing the methodology and in silico solutions to mine biological data and processes, for knowledge
discovery. In the era of molecular diagnostics, targeted drug design and Big Data for personalized or even precision medicine,
computational methods for data analysis are essential for biochemistry, biology, biotechnology, pharmacology, biomedical science,
and mathematics and statistics. Bioinformatics and Computational Biology are essential for making sense of the molecular data from
many modern high-throughput studies of mice and men, as well as key model organisms and pathogens. This Encyclopedia spans
basics to cutting-edge methodologies, authored by leaders in the field, providing an invaluable resource to students as well as
scientists, in academia and research institutes as well as biotechnology, biomedical and pharmaceutical industries.
Navigating the maze of confusing and often contradictory jargon combined with a plethora of software tools is often confusing
for students and researchers alike. This comprehensive and unique resource provides up-to-date theory and application content to
address molecular data analysis requirements, with precise definition of terminology, and lucid explanations by experts.
No single authoritative entity exists in this area, providing a comprehensive definition of the myriad of computer science,
information technology, mathematics, statistics, and biotechnology terms used by scientists working in bioinformatics and
computational biology. Current books available in this area as well as existing publications address parts of a problem or provide
chapters on the topic, essentially addressing practicing bioinformaticists or computational biologists. Newcomers to this area
depend on Google searches leading to published literature as well as several textbooks, to collect the relevant information.
Although curricula have been developed for Bioinformatics education for two decades now (Altman, 1998), offering education in
bioinformatics continues to remain challenging from the multidisciplinary perspective, and is perhaps an NP-hard problem (Ranganathan,
2005). A minimum Bioinformatics skill set for university graduates has been suggested (Tan et al., 2009). The Bioinformatics section of the
Reference Module in Life Sciences (Ranganathan, 2017) commenced by addressing the paucity of a comprehensive reference book, leading
to the development of this Encyclopedia. This compilation aims to fill the “gap” for readers with succinct and authoritative descriptions of
current and cutting-edge bioinformatics areas, supplemented with the theoretical concepts underpinning these topics.
This Encyclopedia comprises three sections, covering Methods, Topics and Applications. The theoretical methodology under-
pinning BCB are described in the Methods section, with Topics covering traditional areas such as phylogeny, as well as more recent
areas such as translational bioinformatics, cheminformatics and computational systems biology. Additionally, Applications will
provide guidance for commonly asked “how to” questions on scientific areas described in the Topics section, using the methodology
set out in the Methods section. Throughout this Encyclopedia, we have endeavored to keep the content as lucid as possible, making
the text “… as simple as possible, but not simpler,” attributed to Albert Einstein. Comprehensive chapters provide overviews while
details are provided by shorter, encyclopedic chapters.
During the planning phase of this Encyclopedia, the encouragement of Elsevier’s Priscilla Braglia and the constructive com-
ments from no less than ten reviewers lead our small preliminary editorial team (Christian Schönbach, Kenta Nakai and myself) to
embark on this massive project. We then welcomed one more Editor-in-Chief, Michael Gribskov and three section editors, Mario
Cannataro, Bruno Gaeta and Asif Khan, whose toils have results in gathering most of the current content, with all editors reviewing
the submissions. Throughout the production phase, we have received invaluable support and guidance as well as milestone
reminders from Paula Davies, for which we remain extremely grateful.
Finally we would like to acknowledge all our authors, from around the world, who dedicated their valuable time to share their
knowledge and expertise to provide educational guidance for our readers, as well as leave a lasting legacy of their work.
We hope the readers will enjoy this Encyclopedia as much as the editorial team have, in compiling this as an ABC of
bioinformatics, suitable for naïve as well as experienced scientists and as an essential reference and invaluable teaching guide for
students, post-doctoral scientists, senior scientists, academics in universities and research institutes as well as pharmaceutical,
biomedical and biotechnological industries. Nobel laureate Walter Gilbert predicted in 1990 that “In the year 2020 you will be
able to go into the drug store, have your DNA sequence read in an hour or so, and given back to you on a compact disk so you can
analyze it.” While technology may have already arrived at this milestone, we are confident one of the readers of this Encyclopedia
will be ready to extract valuable biological data by computational analysis, resulting in biomedical and therapeutic solutions,
using bioinformatics to “measure” health for early diagnosis of “disease.”

References

Altman, R.B., 1998. A curriculum for bioinformatics: the time is ripe. Bioinformatics. 14 (7), 549–550.
Ranganathan, S., 2005. Bioinformatics education–perspectives and challenges. PLoS Comput Biol 1 (6), e52.
Tan, T.W., Lim, S.J., Khan, A.M., Ranganathan, S., 2009. A proposed minimum skill set for university graduates to meet the informatics needs and challenges of the “-omics”
era. BMC Genomics. 10 (Suppl 3), S36.
Ranganathan, S., 2017. Bioinformatics. Reference Module in Life Sciences. Oxford: Elsevier.

Shoba Ranganathan

xxi
Another Random Scribd Document
with Unrelated Content
 EVENING. 211 Oh! receive me, thou, who hast welcomed,
with open arms, in joy and sorrow, the generations that are past.
Ah, how often has a swarm of children clustered about this
patriarchal throne! Here, perhaps, in gratitude for her Christmas-gift,
with the warm round cheek of childhood—has my beloved piously
kissed the withered _ hand of her grandsiré> Maiden, I feel thy spirit
of abundance and order breathe round me—that spirit which daily
instructs thee like a mother—which bids thee spread the cloth neatly
upon the table and curl the sand at thy feet. Dear hand! so godlike!
you make the hut a heaven ; and here—[He lifts up a bed-curtain] |
— what blissful tremor seizes me! Here could I linger for whole
hours! Nature! This angel from birth you shaped, here,inairydreams.
Herelaythechild ! itsgentle bosom filled with warm life; and here,
with weavings of hallowed purity, the divine image developed itself.
And thou, what has brought thee hither? How deeply moved I feel!
What wouldst thou here? Why grows thy heart so heavy ? Miserable
Faust, I no longer know thee. . Am Tin an enchanted atmosphere?” I
panted so for instant enjoyment, and feel myself dissolving into a
dream of love. Are we the sport of every pressure of the air? And if
she entered this very moment, how wouldst thou atone for thy guilt!
The big boaster! alas, how small! would lie, dissolved away, at her
feet. 4
 212 ABEND. Mephistopheles. Geschwind! Ich seh’ sie unten
kommen, Faust. Fort! Fort! Ich kehre nimmermehr ! 2378
Mephistopheles. Hier ist ein Kästchen, leidlich schwer, Ich hab’s wo
anders hergenommen, Stellt’s hier nur immer in den Schrein, Ich
schwör’ euch, ihr vergehn die Sinnen: Ich that euch ‚Sächelchen
hinein, 2380 Um eine Andre zu gewinnen. Zwar Kind ist Kind, und
Spiel ist Spiel. Faust. Ich weisz nicht, soll ich ? Mephistopheles. Fragt
ihr viel ? Meint ihr vielleicht den Schatz zu wahren ? Dann rath’ ich
eurer Lüsternheit, 2385 Die liebe schöne Tageszeit Und mir die
weitre Müh zu sparen. Ich hoff’ nicht, dasz ihr geizig seid! Ich kratz’
den Kopf, reib’ an den Händen— [Er stellt das Kästchen in den
Schrein und drückt das Schlosz wieder zu.] Nur fort! Geschwind !—
2396 Um euch das süsze junge Kind Nach Herzens Wunsch und Will’
zu wenden ; Und ihr seht drein, Als solltet ihr in den Hörsaal hinein,
Als stünden grau leibhaftig vor euch da 2395 Physik und
Metaphysika! Nur fort !— [ 4b.] Margarete (mit einer Lampe). Es ist
so schwiil, so dumpfig hie, [Sie macht das Fenster auf. | Und ist
doch eben so warm nicht drausz. Es wird mir so, ich weisz nicht wie
—>
 EVENING. 213 Mephistopheles, Quick ! I see her coming
below. Faust. Away, away! Ireturn no more. Mephistopheles. Here is
a casket tolerably heavy; I took it from somewhere else. Only place
it instantly in the press here. I.swear to you, she will be fairly beside
herself. I put baubles in it to win by it another; but child is child, and
play is play. Faust. I know not— shall I? Mephistopheles. Is that a
thing to ask about? Perchance you mean to keep the treasure for
yourself ? In that case I advise your covetousness to spare yourself
the precious hours, and further trouble tome. Ihope you are not
avaricious. I scratch my head, rub my hands[He places the casket in
the press and closes the lock. | But away, quick !—to bend the sweet
young creature to your heart’s desire; and now you look as if you
were going to the lecture-room—as if Physic and Metaphysic were
standing grey and bodily before you there. But | away ! [Exeunt.]
Margaret (with a lamp). It feels so close, so sultry here.” [She opens
the window.] And yet it is not so very warm without. I begin to feel
Iknow not how. I wish my mother would.
 OA ABEND. Ich wollt‘, die Mutter kim’ nach Haus, 2400 Mir
läuft ein Schauer übern ganzen Leib— Bin doch ein thöricht
furchtsam Weib! : [Sie fängt an zu singen, indem sie sich auszieht.]
Es war ein König in Thule Gar treu bis an das Grab, Dem sterbend
seine Buhle 2405 Einen goldnen Becher gab. Es ging ihm nichts
darüber, Er leert’ ihn jeden Schmaus ; Die Augen gingen ihm über,
So oft er trank daraus. 2410 Und als er kam zu sterben, Zählt’ er
seine Städt’ im Reich, Gönnt’ Alles seinem Erben, Den Becher nicht
zugleich, Er sasz beim Königsmahle, 2415 Die Ritter um ihn her, Auf
hohem Vätersaale, Dort auf dem Schlosz am Meer. Dort stand der
alte Zecher, Trank letzte Lebensgluth 2420 Und warf den heiligen
Becher Hinunter in die Fluth. Er sah ihn stürzen, trinken Und sinken
tief ins Meer. Die Augen thäten ihm sinken, 2425 Trank nie einen
Tropfen mehr, [Sie eröffnet den Schrein, ihre Kleider einzurüumen,
und erblickt das Schmuckkästchen, Wie kommt das schöne Kästchen
hier herein ? Ich schlosz doch ganz gewisz den Schrein. Es ist doch
wunderbar! Was mag wohl drinne sein ? Vielleicht bracht’s Jemand
als ein Pfand, 2430 Und meine Mutter lieh darauf, Da hängt ein
Schlüsselchen am Band,
 EVENING. 215 come home. I tremble all over; butIama silly,
timid woman, [She begins to sing as she undresses herself. | SONG.
There was a king in Thule,*? Faithful even to the grave, To whom his
dying mistress Gave a golden goblet. He prized nothing above it; He
emptied it at every feast ; His eyes overflowed as often As he drank
out of it. And when he came to die, He reckoned up the cities in his
kingdom ; He grudged none of them to his heir, But not so with the
goblet. He sat at the royal banquet, With his knights around him, In
his proud ancestral hall, there In his castle on the sea. There stood
the old carouser, Took a parting draught of life’s glow, And threw the
hallowed goblet Down into the waves. He saw it splash, fill, and sink
Deep into the sea ; His eyes sank, he never Drank a drop more. [She
opens the press to put away her clothes, and perceives the casket. |
How came this beautiful casket here? I am sure I locked the press.
It is very strange! What is in it, I wonder? Perhaps someone brought
it as a pledge, and my mother lent upon it. A little key hangs by the
 216 ABEND. Ich denke wohl, ich mach’ es auf! Was ist das?
Gott im Himmel ! Schau, So was hab’ ich mein’ Tage nicht gesehn !
2435 Ein Schmuck ! Mit dem könnt eine Edelfrau Am höchsten
Feiertage gehn. Wie sollte mir die Kette stehn ? Wem mag die
Herrlichkeit gehören ? [Sie putzt sich damit auf und tritt vor den
Spiegel] Wenn nur die Ohrring’ meine wären ! 2440 Man sieht doch
gleich ganz anders drein, Was hilft euch Schönheit, junges Blut ? *
Das ist wohl Alles schön und gut, Allein man läszt’s auch Alles sein ;
Man lobt euch halb mit Erbarmen. 2415 Nach Golde drängt, Am
Golde hängt Doch Alles. Ach, wir Armen!
 EVENING. 217 ribbon; I have a good mind to open it. What
is this? Good heavens! Look! I have never seen anything like itin my
life. A set of trinkets! a noble dame might wear such on the highest
festival. How would the chain become me? To whom may this
splendour belong? [She adorns herself with them, and steps before
the looking-glass. | If the earrings were but mine! One cuts quite a
dif. ferent figure in them. What avails your beauty and your youth?
That may be all pretty and good, but one leaves it alone. You are
praised, half in pity. After gold all press, all are attached to gold.
Alas, we poor ones !
 SPAZIERGANG, Faust in Gedanken auf und ab gehend. Zu
ihm MEPHISTOPHELES, Mephistopheles. B™ aller verschmähten
Liebe! Beim höllischen Elemente! Ich wollt’, ich wüszte was Aergers,
dasz ich's fluchen könnte! 2450 Faust. Was hast? Was kneipt dich
denn so sehr? So kein Gesicht sah ich in meinem Leben !
Mephistopheles. Ich möcht’ mich gleich dem Teufel übergeben,
Wenn ich nur selbst kein Teufel wär’! Faust. Hat sich dir was im Kopf
verschoben ? 2455 Dich kleidet’s, wie ein Rasender zu toben!
Mephistopheles. Denkt nur, den Schmuck, für Gretchen angeschafft,
Den hat ein Pfaff hinweggerafft — Die Mutter kriegt das Ding zu
schauen, Gleich fängt’s ihr heimlich an zu grauen: 2460 Die Frau hat
gar einen feinen Geruch, Schnuffelt immer im Gebetbuch Und
riecht’s einem jeden Möbel an, Ob das Ding heilig ist oder profan ;
Und an dem Schmuck da spürt sie’s klar, 2465
 A PROMENADE. Faust walking up and down thoughtfully. To
him MEPHISTOPHELES, Mephistopheles. Yall despised love! By the
flames of hell! Would that I knew something worse to curse by !
Faust. What is the matter? What is it that pinches you so sharply ? I
never saw such a face in my life! Mephistopheles. I could give myself
to the devil directly, were I no devil myself. Faust. Is your brain
disordered? It becomes you truly, to rave like a madman.
Mephistopheles. Oniy think! A priest has carried off the jewels
provided for Margaret. The mother gets sight of the thing, and
begins at once to have a secret horror of it. Truly the woman hath a
fine nose, is ever snuflling in her prayer-book, and smells in every
piece of furniture whether the thing be holy or profane; and she
plainly smells out in the jewels, that there was not
 220 SPAZIERGANG. Dasz dabei nicht viel Segen war. Mein
Kind, rief sie, ungerechtes Gut Befängt die Seele, zehrt auf das Blut.
Wollen’s der Mutter Gottes weihen, Wird uns mit Himmelsmanna
erfreuen ! Margretlein zog ein schiefes Maul; Ist halt, dacht’ sie, ein
geschenkter Gaul, Und wahrlich, gottlos ist nicht der, Der ihn so fein
gebracht hierher. Die Mutter liesz einen Pfaffen kommen ; Der hatte
kaum den Spasz vernommen, Liesz sich den Anblick wohl behagen.
Er sprach : So ist man recht gesinnt ! Wer überwindet, der gewinnt.
Die Kirche hat einen guten Magen, Hat ganze Länder aufgefressen
Und doch noch nie sich übergessen ; Die Kirch’ allein, meine lieben
Frauen, Kann ungerechtes Gut verdauen. Faust. Das ist ein
allgemeiner Brauch, Ein Jud’ und König kann es auch,
Mephistopheles. Strich drauf ein Spange, Kett’ und Ring’, Als wären’s
eben Pfifferling’, Dankt’ nicht weniger und nicht mehr, Als ob’s ein
Korb voll Nüsse wir’, Versprach ihnen allen himmlischen Lohn— Und
sie waren sehr erbaut davon, Faust. Und Gretchen ? Mephistopheles.
Sitzt nun unruhvoll, Weisz weder, was sie will noch soll, Denkt ans
Geschmeide Tag und Nacht, Noch mehr an den, der's ihr gebracht,
2470 2475 2480 2485 2490 2495
 A PROMENADE, 921 much blessing in them. “My child,” said
she, “un. righteous wealth ensnares the soul, consumes the blood.
We will consecrate it to the Mother of God; she will gladden us with
heavenly manna!” Margaret made awry face; it is after all, thought
she, a gift horse ; and truly, he cannot be godless, who brought it
here so handsomely. The mother sent for a priest. Scarcely had he
heard the curious story, when the look of it greatly pleased him. He
spoke: “This shows a good disposition ; who overcomes himself,—he
is the victor. The church has a good stomach; she has eaten up
whole countries, and has never yet over-eaten herself; the church
alone, my good women, can digest unrighteous wealth.” Faust. That
is a general custom; a Jew and a King can do it too. Mephistopheles.
So saying he swept off clasp, chain, and ring, as if they were mere
trifles®; thanked them neither more nor less than if it had been a
basket of nuts; promised them all heavenly reward—and very much
edified they were. Faust. And Margaret ? Mephistopheles. Is now
sitting full of restlessness; not knowing what she wants, or what she
should do with herself; thinks day and night on the trinkets, and still
more on him who brought them to her.
 222 SPAZIERGANG. Faust. Des Liebchens Kummer thut mir
leid. Schaff du ihr gleich ein neu Geschmeid! Am ersten war ja so
nicht viel. Mephistopheles. O ja, dem Herrn ist Alles Kinderspiel !
2500 Faust. Und mach und richt’s nach meinem Sinn! Häng dich an
ihre Nachbarin. Sei, Teufel, doch nur nicht wie Brei Und schaff einen
neuen Schmuck herbei ! Mephistopheles. Ja, gnid’ger Herr, von
Herzen gerne. 2505 [Fausr ab.] Mephistopheles. So ein verliebter
Thor verpufft Euch Sonne, Mond und alle Sterne Zum Zeitvertreib
dem Liebchen in die Luft. [Ab.]
 A PROMENADE. 993 Faust, My love’s grief distresses me.
Get her another set immediately. The first was of no great value
after all. Mephistopheles. Oh! to be sure, all is child’s play to the
gentleman ! Faust. Do it, and order it as I wish. Stick close to her
neighbour. Don’t be a milk-and-water devil; and fetch a fresh set of
jewels. Mephistopheles. With all my heart, honoured Sir. [Faust exit.)
Mephistopheles. A love-sick fool like this puffs away into the air, sun,
moon and stars, by way of pastime for his mistress. [Exit.]
 DER NACHBARIN HAUS. Marthe (allein). “OTT verzeih’s
meinem lieben Mann, Er hat an mir nicht wohl gethan ! 2510 Geht
da stracks in die Welt hinein Und läszt mich auf dem Stroh allein.
Thät ihn doch wahrlich nicht betrüben, Thät ihn, weisz Gott, recht
herzlich lieben. [Sie weint.] Vielleicht ist er gar todt !—O Pein ! 2515
Hätt’ ich nur einen Todtenschein ! i . [MARGARETE kommt.]
Margarete. Frau Marthe ! Marthe. Gretelchen, was soll’s ? Margarete.
* Fast sinken mir die Kniee nieder ! Da find’ ich so ein Kästchen
wieder In meinem Schrein, von Ebenholz, 2520 Und Sachen, herrlich
ganz und gar, Weit reicher, als das erste war, Marthe. Das musz sie
nicht der Mutter sagen ; That's wieder gleich zur Beichte tragen.
Margarete. Ach, seh sie nur! Ach, schau sie nur! 2525
 THE NEIGHBOUR’S HOUSE. Martha (alone). OD forgive my
dear husband ; he has not acted well towards me. He goes straight
away into the world, and leaves me quite alone on the straw. Yet
truly I never did anything to vex him; God knows I loved him with all
my heart. (She weeps.) Perhaps he is actually dead! Oh, torture!—
Had I but a certificate of his death ! MARGARET enters. Margaret.
Dame Martha! Martha. What is the matter, Margaret ? Margaret. My
knees almost sink under me! I have found just such ‘another casket
of ebony in my press, and things quite grand, far costlier than the
first. Martha. You must say nothing about it to your mother; she
would carry it at once to the confessional again. Margaret. Now, only
see! do but look at them ! Q
 226 DER NACHBARIN HAUS. Marthe (putat sie auf). O du
gliicksel’ge Kreatur ! Margarete. Darf mich leider nicht auf der
Gassen Noch in der Kirche mit sehen lassen. Marthe. Komm du nur
oft zu mir heriiber Und leg den Schmuck hier heimlich an ; 2530
Spazier ein Stündchen lang dem Spiegelglas vorüber, Wir haben
unsre Freude dran; Und dann giebt’s einen Anlasz, giebt’s ein Fest,
"."... FÜ Wo man’s so nach und nach den Leuten sehen läszt, Ein
Kettchen erst, die Perle dann ins Ohr; 2535 Die Mutter sieht's wohl
nicht, man macht ihr auch was vor. Margarete. Wer konnte nur die
beiden Kästchen bringen ? Es geht nicht zu mit rechten Dingen ! [Es
klopft.] Ach Gott, mag das meine Mutter sein? Marthe (durchs
Vorhiingel guckend). Es ist ein fremder Herr—Herein ! 2540
[MrriistoPHELEs tritt auf. ] Mephistopheles. Bin so frei, grad herein
zu treten, e Musz bei den Frauen Verzeihn erbeten. [Tritt ehrerbietig
vor MARGARETEN zurück.) Wollte nach Frau Marthe Schwerdtlein
fragen ! Marthe. Ich bin’s. Was hat der Herr zu sagen P
 THE NEIGIIBOUR’S HOUSE. 227 Martha (dresses her up in
them). Oh! you happy creature. Margaret. Unfortunately, I must not
be seen in them in the street, nor in the church. Martha. Do but
come over frequently to me, and put on the trinkets here in private;
walk a little hour up and down before the looking-glass ; we shall
have our enjoyment in that. And then an occasion offers, a holiday
happens, when, little by little, one lets folks see them ; —first a
chain, then the pearl in the ear. Your mother will probably not
observe it, or one may make some pretence to her. Margaret. But
who could have brought the two caskets? There is something
uncanny about it. [Someone knocks. ] Good God! can that be my
mother ? Martha (looking through the little curtain). It is a stranger.
Come in! MEPHISTOPHELES enters. Mephistopheles. I have made
free to come in at once; I have to beg pardon of the ladies. [He
steps back respectfully on seeing Marcarnr.] I came to inquire after
Mrs. Martha Schwerdtlein. Martha. Iam she. What is your pleasure,
Sir?
 228 DER NACHBARIN HAUS, Mephistopheles (leise zu ihr).
Ich kenne sie jetzt, mir ist das genug; Sie hat da gar vornehmen
Besuch. Verzeiht die Freiheit, die ich genommen, Will nach Mittage
wiederkommen. Marthe (laut). Denk, Kind, um Alles in der Welt! Der
Herr dich für ein Fräulein hält. Margarete. Ich bin ein armes junges
Blut; Ach Gott! Der Herr ist gar zu gut: Schmuck und Geschmeide
sind nicht mein. Mephistopheles. Ach, es ist nicht der Schmuck allein
; Sie hat ein Wesen, einen Blick, so scharf ! Wie freut mich’s. dasz
ich bleiben darf. Marthe. Was bringt er denn? Verlange sehr—
Mephistopheles. yo Ich wollt’, ich hätt’ eine frohere Mär’! Ich hoffe,
sie läszt mich’s drum nicht büszen : Ihr Mann ist todt und läszt sie
grüszen. Marthe. Ist todt? Das treue Herz! O weh! Mein Mann ist
todt! Ach, ich vergeh’ ! Margarete. Ach, liebe Frau, verzweifelt nicht!
Mephistopheles. So hört die traurige Geschicht’ ! 2545 2550 2555
2560
 TILE NEIGHBOUR’S HOUSE. 229 Mephistopheles (aside to
her). I know you now—that is enough. You havea visitor of
distinction there. Excuse the liberty I have taken. I will call again in
the afternoon. Martha (aloud). Only think, child—of all things in the
world! This gentleman takes you for a lady. Margaret. I am a poor
young creature. Oh! Heavens, the gentleman is too obliging. The
jewels and ornaments are none of mine. Mephistopheles. Ah! it is
not the jewels alone. You have a mien, a look, so striking. How glad
Iam that I may stay. Martha. What do you bring then? Iam very
curious— Mephistopheles. I wish I had better news! I hope you will
not make me suffer for it. Your husband is dead, and sends you his
greeting. Martha. Is dead? The good soul! Oh, woe is me! My
husband is dead! Ah, I shall die! Margaret. Ah, dearest dame, don’t
despair. Mephistopheles. Listen to the melancholy tale.
 230 DER NACHBARIN HAUS. Margarete. Ich möchte drum
mein’ Tag’ nicht lieben,, 5»: 2565 Würde mich Verlust zu Tode
betrüben. a Mephistopheles. Freud’ musz Leid, Leid musz Freude
haben. Marthe. Erzählt mir seines Lebens Schlusz ! Mephistopheles.
Er liegt in Padua begraben Beim heiligen Antonius, 2570 An einer
wohlgeweihten Stätte Zum ewig kühlen Ruhebette. Marthe. Habt ihr
sonst nichts an mich zu bringen ? Mephistopheles. Ja, eine Bitte,
grosz und schwer > Lasz sie doch ja für ihn dreihundert Messen
singen! 2575 Im Uebrigen sind meine Taschen leer. Marthe. Was!
Nicht ein Schaustück, kein Geschmeid, Was jeder Handwerksbursch
im Grund des Säckels spart, Zum Angedenken aufbewahrt, Und
lieber hungert, lieber bettelt ? 2580 Mephistopheles. Madam, es thut
mir herzlich leid; Allein er hat sein Geld wahrhaftig nicht verzettelt.
Auch er bereute seine Fehler sehr, Ja, und bejammerte sein Unglück
noch viel mehr. Margarete. Ach! Dasz die Menschen so unglücklich
sind! 2585 Gewisz, ich will für ihn manch Requiem noch beten.
 THE NEIGHBOUR’S HOUSE, 231 Margaret. For this reason I
should wish never to be in love for all the days of my life. The loss
would grieve me to death. Mephistopheles. Joy must have sorrow—
sorrow, joy. Martha. Relate to me the close of his life.
Mephistopheles. He lies buried in Padua at St. Antony’s, in a
wellconsecrated spot for an eternally cool bed of rest. Martha. Have
you nothing else for me? : Mephistopheles. Yes, a request, big and
heavy; be sure to have three hundred masses sung forhim! For the
rest, my pockets are empty. Bst artha. What! Not a medal? Not a
trinket? what every journeyman spares at the bottom of his wallet,
keeping it as a token, and rather starves, rather begs—
Mephistopheles. Madam, I am very sorry. But he really has not
squandered away his money. He also bitterly repented of his sins;
ay, and bewailed his ill-luck still more. Margaret. Ah! that mortals
should be so unfortunate! Assuredly I will say many a prayer for his
soul.
 } Wi 232 DER NACHBARIN HAUS. Mephistopheles. Ihr
wäret werth, gleich in die Eh’ zu treten: Ihr seid ein liebenswürdig
Kind. Margarete. Ach nein, das geht jetzt noch nicht an.
Mephistopheles. Ist’s nicht ein Mann, sei’s derweil ein Galan, 2590 ’g
ist eine der gröszten Himmelsgaben ! So ein lieb Ding im Arm zu
haben. Margarete, m Das ist des Landes nicht der Brauch. (,"
Mephistopheles. Brauch oder nicht! Es giebt sich auch. Marthe.
Erzählt mir doch ! Mephistopheles. Ich stand an seinem Sterbebette,
2595 Es war was besser als von Mist, Von halbgefaultem Stroh;
allein er starb als Christ Und fand, dasz er weit mehr noch auf der
Zeche hätte. Wie, rief er, musz ich mich von Grund aus hassen, So
mein Gewerb, mein Weib so zu verlassen ! 2600 Ach, die Erinn’rung
tödtet mich. “Vergäb' sie mir nur noch in diesem Leben !— Marthe
(weinend). Der gute Mann! Ich hab’ ihm längst; vergeben.
Mephistopheles, Allein, weisz Gott, sie war mehr Schuld als ich.
 THE NEIGHBOUR’S HOUSE. 233 Mephistopheles. You
deserve to be married directly. You are a loveable child. Margaret.
Oh, no} that would not do for the present. Mephistopheles. If not a
husband, then a gallant in the meantime. It is one of the best gifts
of heaven to have so sweet a thing in one’s arms. Margaret. That is
not the custom in this country. Mephistopheles. Custom or not! Such
things do come to pass though. Martha. But relate to me!
Mephistopheles. I stood by his death-bed. It was somewhat better
than dung,—of half-rotten straw; but he died like a Christian, and
found that he had still much more upon his score. How thoroughly,
he cried, must I detest myself—to run away from my business and
my wife in such a manner. Oh! the recollection is death to me. If she
would but forgive me in this life !— Martha (weeping). The good
man! I have long since forgiven him. Mephistopheles. But, God
knows, she was more in fault than I.
 224 DER NACHBARIN HAUS. Marthe. Das lügt er! Was, am
Rand des Grabs zu lügen ! 2605 Mephistopheles. fa" Er fabelte
gewisz in letzten Zügen, Ar @ Wenn ich nur halb ein Kenner bin. Ich
hatte, sprach er, nicht zum Zeitvertreib zu gaffen, Erst Kinder und
dann Brod für sie zu schaffen, Und Brod im allerweitsten Sinn, 2610
Und konnte nicht einmal mein Theil in Frieden essen. Marthe. Hat er
so aller Treu’, so aller Lieb’ vergessen, u“; Der Plackerei bei Tag und
Nacht! = jar” | \ Mephistopheles. Nicht doch, er hat euch herzlich
dran gedacht, Er sprach : Als ich nun weg von Malta ging, 2615 Da
betet’ ich für Frau und Kinder brünstig ; Uns war denn auch der
Himmel günstig, Dasz unser Schiff ein türkisch Fahrzeug fing, Das
einen Schatz des groszen Sultans führte, Da ward der Tapferkeit ihr
Lohn, 2629 Und ich empfing denn auch, wie sich’s gebührte, Mein
wohlgemessnes Theil davon. Marthe. Ei wie? Ei wo? Hat er’s
vielleicht vergraben ? Mephistopheles. Wer weisz, wo nun es die vier
Winde haben ! Ein schönes Fräulein nahm sich seiner an, 2625 Als er
in Napel fremd umherspazierte ; Sie hat an ihm viel Lieb’s und Treu’s
gethan, Dasz er’s bis an sein selig Ende spürte, Marthe. Der Schelm !
Der Dieb an seinen Kindern !
 THE NEIGHBOUR’S HOUSE. 235 Martha. He lied then!
What, tell lies on the brink of the grave! Mephistopheles. 2 He
certainly fabled with his last breath, if I am but half a judge. I, said
he, had no occasion to gape for pastime—first to get children, and
then bread for them —and bread in the widest sense,—and could
not even eat my share in peace. Martha. Did he thus forget all my
fidelity, all my love—my drudgery by day and night? @
Mephistopheles. Not so; he affectionately reflected on it. He said:
When I left Malta, I prayed fervently for my wife and children ; and
heaven was so far favourable, that our ship took a Turkish vessel,
which carried a treasure of the great sultan. Bravery had its reward,
and, as was no more than right, I got my fair share of it. Martha.
How! Where! Can he have buried it? Mephistopheles. Who knows
where it is now scattered to the four winds of heaven! A fair damsel
took an interest in him as he was strolling about, a stranger, in
Naples. She showed great fondness and fidelity towards him ; so
much so, that he felt it even unto his blessed end. ‘ Martha. The
villain! The robber of his children! And all the
 236 DER NACHBARIN HAUS. Auch alles Elend, alle Noth
Konnt’ nicht sein schändlich Leben hindern I x Mephistopheles. Ja
seht! Dafür ist er nun todt. Wär’ ich nun jetzt an eurem Platze, an
Betraurt’ ich ihn ein züchtig Jahr, Visirte dann unterweil nach einem
neuen Schatze. Marthe. Ach Gott, wie doch mein erster war, Find’ ich
nicht leicht auf dieser Welt den andern! Es konnte kaum ein herziger
Närrchen sein. Er liebte nur das allzu viele Wandern Und fremde
Weiber und fremden Wein Und das verfluchte Würfelspiel.
Mephistopheles. Nun, nun, so konnt’ es gehn und stehen, Wenn er
euch ungefähr so viel Von seiner Seite nachgesehen. Ich schwör'
euch zu, mit dem Beding Wechselt’ ich selbst mit euch den Ring !
Marthe. O, es beliebt dem Herrn zu scherzen ! Mephistopheles (für
sich). Nun mach’ ich mich bei Zeiten fort! Die hielte wohl den Teufel
selbst beim Wort. 2630 2635 2640 2645 2649 (Zu GrEICHEN.) Wie
steht es denn mit ihrem Herzen? Margarete. Was meint der Herr
damit ? Mephistopheles (für sich). Du gut’s, unschuldig’s Kind !
(Zaut.) Lebt wohl, ihr Frau’n ! Margarete. Lebt wohl !
 THE NEIGHBOUR’S HOUSE. 237 wretchedness, all the
poverty, could not check his scandalous life. Mephistopheles, But you
see, he died in consequence of it. Now, were IT in your place, I
would mourn him for one chaste year, and have an eye towards a
new sweetheart in the mean- — time. Martha. Oh, God! but I shall
not easily in this world find another like my first. There could hardly
be a sweeter little fool. He only loved too much roaming about, and
foreign women, and foreign wine, and the cursed dicing.
Mephistopheles. Well, well, things might have gone on very well, if
he, on his part, only had the same indulgence for you. I swear, upon
this condition, I would change rings , with you myself!” Martha. Oh,
the gentleman is pleased’ to jest. Mephistopheles (aside). Now it is
full time to be off. I dare say she would take the devil himself at his
word—(To MARGARET.) How goes it with your heart? Margaret.
What do you mean, Sir? Mephistopheles (aside). Good, innocent
child.—(Aloud.) Farewell, ladies ! Margaret. Farewell !
 238 DER NACHBARIN HAUS. Marthe. O, sagt mir doch
geschwind! Ich méchte gern ein Zeugnisz haben, Wo, wie und wann
mein Schatz gestorben und begraben. Ich bin von je der Ordnung
Freund gewesen, 2655 Mécht’ ihn auch todt im Wochenblättchen
lesen, Mephistopheles. Ja, gute Frau, durch zweier Zeugen Mund
Wird allerwegs die Wahrheit kund; Habe noch gar einen feinen
Gesellen, Den will ich euch vor den Richter stellen. 2660 Ich bring’
ihn her. Marthe. O, thut das ja! Mephistopheles. Und hier die
Jungfrau ist auch da ?— Ein braver Knab’! Ist viel gereist, Fräuleins
alle Höflichkeit erweist. Margarete. ' Müszte vor dem Herren
schamroth werden. 2665 Mephistopheles. Vor keinem Könige der
Erden. Marthe. Da hinterm Haus in meinem Garten Wollen wir der
Herrn heut Abend warten,
 THE NEIGHBOUR’S HOUSE. 239 Martha. Oh, but tell me
quickly! I should like to have a certificate where, how, and when my
love died and was buried. I was always a friend to regularity, and
should like to read his death in the weekly paper. Mephistopheles.
Ay, my good madam, the truth is manifested by the testimony of two
witnesses '” all the world over; and I have a gallant companion,
whom I will bring before the judge for you. I will fetch him here.
Martha. Oh, pray do! Mephistopheles. And the young lady will be
here too?—A fine lad! Has travelled much, and shows all possible
politeness to - the ladies. Margaret. I should be covered with
confusion in the presence of the gentleman. Mephistopheles. In the
presence of no king on earth. Martha. Behind the house there, in my
garden, we shall expect you both this evening.
 STRASZE. Faust. MEPHISTOPHELES. Faust. \ N JIE ist's?
Will's fördern ? Will’s bald gehn P Mephistopheles. Ah bravo! Find’
ich euch in Feuer? 2670 In kurzer Zeit ist Gretchen euer. Heut Abend
sollt ihr sie bei Nachbars Marthen sehn: Das ist ein Weib wie
auserlesen Zum Kuppler- und Zigeunerwesen ! Faust. So recht !
Mephistopheles. Doch wird auch was von uns begehrt. 2675 Faust.
Ein Dienst ist wohl des andern werth. Mephistopheles. Wir legen nur
ein gültig Zeugnisz nieder, Dasz ihres Ehherrn ausgereckte Glieder In
Padua an heil’ger Stätte ruhn, Faust. Sehr klug! Wir werden erst die
Reise machen müssen ! 2689
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