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Methods in
Molecular Biology 2254

Haiming Cao Editor

Functional
Analysis of Long
Non-Coding
RNAs
Methods and Protocols
METHODS IN MOLECULAR BIOLOGY

Series Editor
John M. Walker
School of Life and Medical Sciences
University of Hertfordshire
Hatfield, Hertfordshire, UK

For further volumes:


http://www.springer.com/series/7651
For over 35 years, biological scientists have come to rely on the research protocols and
methodologies in the critically acclaimed Methods in Molecular Biology series. The series was
the first to introduce the step-by-step protocols approach that has become the standard in all
biomedical protocol publishing. Each protocol is provided in readily-reproducible step-by-
step fashion, opening with an introductory overview, a list of the materials and reagents
needed to complete the experiment, and followed by a detailed procedure that is supported
with a helpful notes section offering tips and tricks of the trade as well as troubleshooting
advice. These hallmark features were introduced by series editor Dr. John Walker and
constitute the key ingredient in each and every volume of the Methods in Molecular Biology
series. Tested and trusted, comprehensive and reliable, all protocols from the series are
indexed in PubMed.
Functional Analysis of Long
Non-Coding RNAs

Methods and Protocols

Edited by

Haiming Cao
Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health,
Bethesda, MA, USA
Editor
Haiming Cao
Cardiovascular Branch
National Heart, Lung and Blood
Institute
National Institutes of Health
Bethesda, MA, USA

ISSN 1064-3745 ISSN 1940-6029 (electronic)


Methods in Molecular Biology
ISBN 978-1-0716-1157-9 ISBN 978-1-0716-1158-6 (eBook)
https://doi.org/10.1007/978-1-0716-1158-6

© Springer Science+Business Media, LLC, part of Springer Nature 2021


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Preface

Although 2% of the human genome is sufficient to encode all protein-coding genes, a vast
majority of the genome can be transcribed giving rise to 60,000 to 100,000 long noncoding
RNAs (lncRNAs). Mounting evidence supports the notion that lncRNAs play a vital role in
diverse biological progresses, and their dysfunctions have been implicated in a growing list of
human diseases. Studying the function of lncRNAs thus has great potential to quickly fill
knowledge gaps in molecular biology and to identify novel therapeutic targets for human
diseases. However, it remains difficult to identify which lncRNAs are important and how
they carry out their functions. The challenges are threefold. First, compared to protein-
coding genes, our current understanding of the sequence-function relationship of lncRNAs
is limited, and it is difficult to deduce the function of lncRNAs based on their primary
sequence. More robust bioinformatics analyses are often needed to select lncRNAs for
downstream experimental interrogation. Second, the annotation of human lncRNAs is far
from complete. Third, lncRNAs often exercise their function through unique mechanisms
and novel approaches, and systems are required to define their functional importance and
molecular mechanisms. For example, most lncRNAs studied so far exert their function
through their protein-binding partners whose identification is crucial to define a lncRNA’s
mechanism of action. Furthermore, most human lncRNAs are non-conserved and new
models are required to define their physiological function. This book addresses these
fundamental challenges by presenting a comprehensive bioinformatic (Chapters 1–8) and
experimental (Chapters 9–21) toolbox for prioritizing, annotating, and functionally analyz-
ing lncRNAs. It is my hope that this book will provide a timely and convenient resource to
facilitate the identification and characterization of disease-associated human lncRNAs,
which would shed light on their role in biology and pathophysiology and ultimately lead
to novel therapeutic approaches targeting lncRNAs for the amelioration of human diseases.

Bethesda, MD, USA Haiming Cao

v
Contents

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix

1 Bioinformatics Approaches for Functional Prediction of Long


Noncoding RNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Fayaz Seifuddin and Mehdi Pirooznia
2 Visualization of lncRNA and mRNA Structure Models
Within the Integrative Genomics Viewer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Steven Busan and Kevin M. Weeks
3 RNA Coding Potential Prediction Using Alignment-Free
Logistic Regression Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Ying Li and Liguo Wang
4 Classification of Long Noncoding RNAs by k-mer Content . . . . . . . . . . . . . . . . . . 41
Jessime M. Kirk, Daniel Sprague, and J. Mauro Calabrese
5 Genome-Wide Computational Analysis and Validation of Potential
Long Noncoding RNA-Mediated DNA–DNA–RNA Triplexes
in the Human Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Saakshi Jalali, Amrita Singh, Vinod Scaria, and Souvik Maiti
6 Using INFERNO to Infer the Molecular Mechanisms Underlying
Noncoding Genetic Associations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Alexandre Amlie-Wolf, Pavel P. Kuksa, Chien-Yueh Lee,
Elisabeth Mlynarski, Yuk Yee Leung, and Li-San Wang
7 A Bioinformatic Pipeline to Integrate GWAS and eQTL Datasets
to Identify Disease Relevant Human Long Noncoding RNAs . . . . . . . . . . . . . . . . 93
Yi Chen, Ping Li, and Haiming Cao
8 AnnoLnc: A One-Stop Portal to Systematically Annotate Novel
Human Long Noncoding RNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
De-Chang Yang, Lan Ke, Yang Ding, and Ge Gao
9 Annotation of Full-Length Long Noncoding RNAs with Capture
Long-Read Sequencing (CLS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Sı́lvia Carbonell Sala, Barbara Uszczyńska-Ratajczak,
Julien Lagarde, Rory Johnson, and Roderic Guigo
10 Single-Cell Analysis of Long Noncoding RNAs (lncRNAs) in Mouse
Brain Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Boyang Zhang, Wentao Xu, and James Eberwine
11 Detection and Characterization of Ribosome-Associated Long
Noncoding RNAs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Chao Zeng and Michiaki Hamada
12 Analysis of Annotated and Unannotated Long Noncoding RNAs
from Exosome Subtypes Using Next-Generation RNA Sequencing . . . . . . . . . . . 195
Wittaya Suwakulsiri, Maoshan Chen, David W. Greening,
Rong Xu, and Richard J. Simpson
vii
viii Contents

13 DMS-MaPseq for Genome-Wide or Targeted RNA Structure Probing


In Vitro and In Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Phillip Tomezsko, Harish Swaminathan, and Silvi Rouskin
14 Labeling and Purification of Temporally Expressed RNAs During
the S-Phase of the Cell Cycle in Living Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Matthieu Meryet-Figuiere, Mohamad Moustafa Ali,
Santhilal Subhash, and Chandrasekhar Kanduri
15 A Quick Immuno-FISH Protocol for Detecting RNAs,
Proteins, and Chromatin Modifications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Akiyo Ogawa and Yuya Ogawa
16 M(R)apping RNA–Protein Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Jasmine Barra, Roberto Vendramin, and Eleonora Leucci
17 In Vivo Administration of Therapeutic Antisense Oligonucleotides . . . . . . . . . . . 273
Luisa Statello, Mohamad Moustafa Ali,
and Chandrasekhar Kanduri
18 CRISPR-Mediated Mutagenesis of Long Noncoding RNAs. . . . . . . . . . . . . . . . . . 283
Tomohiro Yamazaki and Tetsuro Hirose
19 In Vivo CRISPR/Cas9-Based Targeted Disruption and Knockin
of a Long Noncoding RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Xi Cheng, Samuel T. Peters, Shondra M. Pruett-Miller,
Thomas L. Saunders, and Bina Joe
20 Genome-Scale Perturbation of Long Noncoding RNA
Expression Using CRISPR Interference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
S. John Liu, Max A. Horlbeck, Jonathan S. Weissman,
and Daniel A. Lim
21 In Vivo Functional Analysis of Nonconserved Human lncRNAs
Using a Humanized Mouse Model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
Yonghe Ma, Cheng-Fei Jiang, Ping Li, and Haiming Cao

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
Contributors

MOHAMAD MOUSTAFA ALI • Department of Medical Biochemistry and Cell Biology, Institute
of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
ALEXANDRE AMLIE-WOLF • Penn Neurodegeneration Genomics Center, University of
Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of
Pathology & Laboratory Medicine, University of Pennsylvania Perelman School of
Medicine, Philadelphia, PA, USA
JASMINE BARRA • Department of Oncology, Laboratory of RNA Cancer Biology, LKI Leuven
Cancer Institute, KU Leuven-University of Leuven, Leuven, Belgium; Laboratory for
Molecular Cancer Biology, Center for Cancer Biology, VIB, Leuven, Belgium
STEVEN BUSAN • Department of Chemistry, University of North Carolina, Chapel Hill, NC,
USA
J. MAURO CALABRESE • Department of Pharmacology, University of North Carolina at
Chapel Hill, Chapel Hill, NC, USA; Curriculum in Bioinformatics and Computational
Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger
Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill,
NC, USA; Curriculum in Pharmacology, University of North Carolina at Chapel Hill,
Chapel Hill, NC, USA
HAIMING CAO • Cardiovascular Branch, National Heart, Lung and Blood Institute,
National Institutes of Health, Bethesda, MD, USA
SÍLVIA CARBONELL SALA • Centre for Genomic Regulation (CRG), The Barcelona Institute of
Science and Technology, Barcelona, Catalonia, Spain
MAOSHAN CHEN • Department of Biochemistry and Genetics, La Trobe Institute for
Molecular Science (LIMS), La Trobe University, Melbourne, VIC, Australia; Australian
Centre for Blood Diseases, Alfred Hospital, Monash University, Melbourne, VIC, Australia
YI CHEN • Cardiovascular Branch, National Heart, Lung and Blood Institute, National
Institutes of Health, Bethesda, MD, USA
XI CHENG • Department of Physiology and Pharmacology, University of Toledo College of
Medicine and Life Sciences, Toledo, OH, USA
YANG DING • Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced
Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking
University, Beijing, China; State Key Laboratory of Protein and Plant Gene Research at
School of Life Sciences, Peking University, Beijing, China
JAMES EBERWINE • Department of Systems Pharmacology and Translational Therapeutics,
University of Pennsylvania Perlman School of Medicine, Philadelphia, PA, USA
GE GAO • Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced
Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking
University, Beijing, China; State Key Laboratory of Protein and Plant Gene Research at
School of Life Sciences, Peking University, Beijing, China
DAVID W. GREENING • Department of Biochemistry and Genetics, La Trobe Institute for
Molecular Science (LIMS), La Trobe University, Melbourne, VIC, Australia; Molecular
Proteomics, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia

ix
x Contributors

RODERIC GUIGÓ • Centre for Genomic Regulation (CRG), The Barcelona Institute of
Science and Technology, Barcelona, Catalonia, Spain; Universitat Pompeu Fabra (UPF),
Barcelona, Catalonia, Spain
MICHIAKI HAMADA • AIST-Waseda University Computational Bio Big-Data Open
Innovation Laboratory (CBBD-OIL), Tokyo, Japan; Faculty of Science and Engineering,
Waseda University, Tokyo, Japan; Artificial Intelligence Research Center, National
Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan; Institute
for Medical-Oriented Structural Biology, Waseda University, Tokyo, Japan; Graduate
School of Medicine, Nippon Medical School, Tokyo, Japan
TETSURO HIROSE • Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
MAX A. HORLBECK • Department of Cellular and Molecular Pharmacology, University of
California, San Francisco, CA, USA; Howard Hughes Medical Institute, University of
California, San Francisco, CA, USA; California Institute for Quantitative Biomedical
Research, University of California, San Francisco, CA, USA; Center for RNA Systems
Biology, University of California, San Francisco, CA, USA
SAAKSHI JALALI • CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi,
India; Reliance Technology Group, Reliance Industries Limited, Navi Mumbai, India
CHENG-FEI JIANG • Cardiovascular Branch, National Heart, Lung and Blood Institute,
National Institutes of Health, Bethesda, MD, USA
BINA JOE • Department of Physiology and Pharmacology, University of Toledo College of
Medicine and Life Sciences, Toledo, OH, USA
RORY JOHNSON • Department of Medical Oncology, Inselspital, University Hospital,
University of Bern, Bern, Switzerland; Department of Biomedical Research (DBMR),
University of Bern, Bern, Switzerland; School of Biology and Environmental Science,
University College Dublin, Dublin, Ireland; Conway Institute of Biomedical and
Biomolecular Research, University College Dublin, Dublin, Ireland
CHANDRASEKHAR KANDURI • Department of Medical Biochemistry and Cell Biology, Institute
of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
LAN KE • Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced
Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking
University, Beijing, China; State Key Laboratory of Protein and Plant Gene Research at
School of Life Sciences, Peking University, Beijing, China
JESSIME M. KIRK • Invitae Corporation, San Francisco, CA, USA; Department of
Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;
Curriculum in Bioinformatics and Computational Biology, University of North Carolina
at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center,
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
PAVEL P. KUKSA • Penn Neurodegeneration Genomics Center, University of Pennsylvania
Perelman School of Medicine, Philadelphia, PA, USA; Department of Pathology &
Laboratory Medicine, University of Pennsylvania Perelman School of Medicine,
Philadelphia, PA, USA
JULIEN LAGARDE • Centre for Genomic Regulation (CRG), The Barcelona Institute of
Science and Technology, Barcelona, Catalonia, Spain
CHIEN-YUEH LEE • Penn Neurodegeneration Genomics Center, University of Pennsylvania
Perelman School of Medicine, Philadelphia, PA, USA; Department of Pathology &
Laboratory Medicine, University of Pennsylvania Perelman School of Medicine,
Philadelphia, PA, USA
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Contributors xi

ELEONORA LEUCCI • Department of Oncology, Laboratory of RNA Cancer Biology, LKI


Leuven Cancer Institute, KU Leuven-University of Leuven, Leuven, Belgium
YUK YEE LEUNG • Penn Neurodegeneration Genomics Center, University of Pennsylvania
Perelman School of Medicine, Philadelphia, PA, USA; Department of Pathology &
Laboratory Medicine, University of Pennsylvania Perelman School of Medicine,
Philadelphia, PA, USA
PING LI • Cardiovascular Branch, National Heart, Lung and Blood Institute, National
Institutes of Health, Bethesda, MD, USA
YING LI • Division of Biomedical Statistics and Informatics, Mayo Clinic College of
Medicine, Rochester, MN, USA
DANIEL A. LIM • Flagship Pioneering, Boston, MA, USA; Department of Neurological
Surgery, University of California, San Francisco, CA, USA; Eli and Edythe Broad Center
of Regeneration Medicine and Stem Cell Research, University of California, San Francisco,
CA, USA; San Francisco Veterans Affairs Medical Center, University of California, San
Francisco, CA, USA
S. JOHN LIU • Department of Neurological Surgery, University of California, San Francisco,
CA, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,
University of California, San Francisco, CA, USA
YONGHE MA • Cardiovascular Branch, National Heart, Lung and Blood Institute,
National Institutes of Health, Bethesda, MD, USA
SOUVIK MAITI • CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi,
India; Academy of Scientific and Innovative Research (AcSIR), CSIR IGIB South
Campus, Delhi, India
MATTHIEU MERYET-FIGUIERE • Department of Medical Biochemistry and Cell Biology,
Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg,
Sweden; Normandie Univ, UNICAEN, INSERM U1086 “ANTICIPE”
(Interdisciplinary Research Unit for Cancers Prevention and Treatment, Axis BioTICLA
“Biology and Innovative Therapeutics for Ovarian Cancers”), Caen, France;
Comprehensive Cancer Centre François Baclesse, UNICANCER, Caen, France
ELISABETH MLYNARSKI • Penn Neurodegeneration Genomics Center, University of
Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of
Pathology & Laboratory Medicine, University of Pennsylvania Perelman School of
Medicine, Philadelphia, PA, USA
AKIYO OGAWA • Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical
Center, Cincinnati, OH, USA
YUYA OGAWA • Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical
Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College
of Medicine, Cincinnati, OH, USA
SAMUEL T. PETERS • Center for Advanced Genome Engineering, St. Jude Children’s Research
Hospital, Memphis, TN, USA
MEHDI PIROOZNIA • Bioinformatics and Computational Biology, National Heart, Lung,
and Blood Institute National Institutes of Health, Bethesda, MD, USA
SHONDRA M. PRUETT-MILLER • Center for Advanced Genome Engineering, St. Jude
Children’s Research Hospital, Memphis, TN, USA
SILVI ROUSKIN • Whitehead Institute, Cambridge, MA, USA
THOMAS L. SAUNDERS • Transgenic Animal Model Core, University of Michigan, Ann Arbor,
MI, USA
xii Contributors

VINOD SCARIA • CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi,
India; Academy of Scientific and Innovative Research (AcSIR), CSIR IGIB South
Campus, Delhi, India
FAYAZ SEIFUDDIN • Bioinformatics and Computational Biology, National Heart, Lung, and
Blood Institute National Institutes of Health, Bethesda, MD, USA
RICHARD J. SIMPSON • Department of Biochemistry and Genetics, La Trobe Institute for
Molecular Science (LIMS), La Trobe University, Melbourne, VIC, Australia
AMRITA SINGH • CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi,
India
DANIEL SPRAGUE • Flagship Pioneering, Boston, MA, USA; Department of Pharmacology,
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger
Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill,
NC, USA; Curriculum in Pharmacology, University of North Carolina at Chapel Hill,
Chapel Hill, NC, USA
LUISA STATELLO • Department of Medical Biochemistry and Cell Biology, Institute of
Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
SANTHILAL SUBHASH • Department of Medical Biochemistry and Cell Biology, Institute of
Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
WITTAYA SUWAKULSIRI • Department of Biochemistry and Genetics, La Trobe Institute for
Molecular Science (LIMS), La Trobe University, Melbourne, VIC, Australia
HARISH SWAMINATHAN • Whitehead Institute, Cambridge, MA, USA
PHILLIP TOMEZSKO • Program in Virology, Harvard Medical School, Boston, MA, USA;
Whitehead Institute, Cambridge, MA, USA
BARBARA USZCZYŃSKA-RATAJCZAK • Institute of Bioorganic Chemistry Polish Academy,
Poznan, Poland
ROBERTO VENDRAMIN • Department of Oncology, Laboratory of RNA Cancer Biology, LKI
Leuven Cancer Institute, KU Leuven-University of Leuven, Leuven, Belgium; Laboratory
for Molecular Cancer Biology, Center for Cancer Biology, VIB, Leuven, Belgium
LIGUO WANG • Division of Biomedical Statistics and Informatics, Mayo Clinic College of
Medicine, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo
Clinic College of Medicine, Rochester, MN, USA
LI-SAN WANG • Penn Neurodegeneration Genomics Center, University of Pennsylvania
Perelman School of Medicine, Philadelphia, PA, USA; Department of Pathology &
Laboratory Medicine, University of Pennsylvania Perelman School of Medicine,
Philadelphia, PA, USA
KEVIN M. WEEKS • Department of Chemistry, University of North Carolina, Chapel Hill,
NC, USA
JONATHAN S. WEISSMAN • Department of Cellular and Molecular Pharmacology, University
of California, San Francisco, CA, USA; Howard Hughes Medical Institute, University of
California, San Francisco, CA, USA; California Institute for Quantitative Biomedical
Research, University of California, San Francisco, CA, USA; Center for RNA Systems
Biology, University of California, San Francisco, CA, USA
RONG XU • Department of Biochemistry and Genetics, La Trobe Institute for Molecular
Science (LIMS), La Trobe University, Melbourne, VIC, Australia
WENTAO XU • Beijing Advanced Innovation Center for Food Nutrition and Human
Health, College of Food Science and Nutritional Engineering, China Agricultural
University, Beijing, China
Contributors xiii

TOMOHIRO YAMAZAKI • Graduate School of Frontier Biosciences, Osaka University, Suita,


Japan
DE-CHANG YANG • Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced
Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking
University, Beijing, China; State Key Laboratory of Protein and Plant Gene Research at
School of Life Sciences, Peking University, Beijing, China
CHAO ZENG • AIST-Waseda University Computational Bio Big-Data Open Innovation
Laboratory (CBBD-OIL), Tokyo, Japan; Faculty of Science and Engineering, Waseda
University, Tokyo, Japan
BOYANG ZHANG • Department of Systems Pharmacology and Translational Therapeutics,
University of Pennsylvania Perlman School of Medicine, Philadelphia, PA, USA; Beijing
Advanced Innovation Center for Food Nutrition and Human Health, College of Food
Science and Nutritional Engineering, China Agricultural University, Beijing, China
Chapter 1

Bioinformatics Approaches for Functional Prediction


of Long Noncoding RNAs
Fayaz Seifuddin and Mehdi Pirooznia

Abstract
There is accumulating evidence that long noncoding RNAs (lncRNAs) play crucial roles in biological
processes and diseases. In recent years, computational models have been widely used to predict potential
lncRNA–disease relations. In this chapter, we systematically describe various computational algorithms and
prediction tools that have been developed to elucidate the roles of lncRNAs in diseases, coding potential/
functional characterization, or ascertaining their involvement in critical biological processes as well as
provide a comprehensive summary of these applications.

Key words LncRNA functional prediction, LncRNA–disease association, LncRNA–protein correla-


tion, LncRNA coding potential, LncRNA Bioinformatics

1 Introduction

Recently, there has been evidence suggesting that long noncoding


RNAs (lncRNAs) can participate in various crucial biological pro-
cesses and can also be used as the most promising biomarkers for
the treatment of certain diseases such as coronary artery disease and
various cancers [1]. Due to costs and time complexity, the number
of possible disease-related lncRNAs that can be verified by
biological experiments is very limited. Therefore, in recent years,
the widespread use of computational models to predict potential
lncRNA–disease associations is common [2, 3]. Developing pow-
erful computational models for potential disease-related lncRNAs
identification would benefit biomarker identification and drug dis-
covery for human disease diagnosis, treatment, prognosis, and
prevention. We systematically describe various computational algo-
rithms and prediction tools to illuminate the roles of lncRNAs in
diseases, and their functional characterization in critical biological
processes. In addition, we present a comprehensive summary of the
tools with references and links to their GitHub or webpages for
implementation. Based on our assessment, these 25 publicly

Haiming Cao (ed.), Functional Analysis of Long Non-Coding RNAs: Methods and Protocols, Methods in Molecular Biology,
vol. 2254, https://doi.org/10.1007/978-1-0716-1158-6_1, © Springer Science+Business Media, LLC, part of Springer Nature 2021

1
2 Fayaz Seifuddin and Mehdi Pirooznia

available tools can be classified into three main categories (Table 1),
lncRNA–disease (n = 11), lncRNA–protein function (n = 7), and
coding potential (n = 4), as well as some tools with hybrid func-
tionality (n = 3). Our description of each tool will include a brief
summary of the methods and its utility. We conclude with discuss-
ing the limitations of these computational methods and future
directions of lncRNA function prediction.

2 LncRNA–Disease Association Tools

Tools in this category operate under the assumption that there is a


semantic similarity among disease and lncRNAs function. Several
studies have indicated that lncRNAs are highly associated with the
occurrence or progression of a wide variety of diseases [4–7]. Tools
in this category such as NBCLDA [8], PADLMHOOI [9],
DCSLDA [10], SIMCLDA [11], TPGLDA [12], PMFILDA
[13], LLCLPLDA [14], BPLLDA [15], Lnc2Cancer [16], TSSR
[17], and ProphTools [18] use lncRNA–disease association infor-
mation, disease similarity, lncRNA–disease correlation, and other
similarity mechanism to construct the lncRNA–disease heteroge-
neous network and implement global network similarity-based
models [19], to predict potential lncRNA–disease associations
(Table 1).

2.1 NBCLDA Naı̈ve Bayesian Classifier used to predict potential LncRNA–Dis-


ease Associations (NBCLDA) [8] is a novel probabilistic model
constructed using a global tripartite network by integrating three
kinds of heterogeneous networks including an lncRNA–disease
association network, an miRNA–disease association network, and
an miRNA–lncRNA interaction network. In addition, a quadruple
global network is appended to the tripartite network developed
above using a more heterogeneous gene–lncRNA interaction net-
work, a gene–disease association network, and a gene–miRNA
interaction network. NBCLDA is assembled on these two newly
constructed global networks.

2.2 PADLMHOOI PADLMHOOI [9] proposes to infer potential associations


between diseases and lncRNA–miRNA pairs. It consists of four
major steps. The first step involves downloading disease–lncRNA,
disease–miRNA, and lncRNA–miRNA associations from various
databases. Using these associations, bipartite networks are con-
structed for each association and eventually integrated into a tripar-
tite network of disease, lncRNA, and miRNA. The second step
involves measuring similarity between diseases, lncRNAs and miR-
NAs including functional similarity. The third step involves adding
weights between known diseases, lncRNAs, and miRNAs to
improve the prediction performance of PADLMHOOI. The fourth
Table 1
Publicly available tools that have been developed to elucidate the roles of lncRNAs in diseases, coding potential/functional characterization, or
ascertaining their involvement in critical biological processes

Methods Authors PMID Year Description URL


Sc- He et al. 30,258,427 2018 A sequence-based predictor for identifying non-coding http://server.malab.cn/Sc_ncDNAPred/
ncDNAPred DNA in Saccharomyces cerevisiae index.jsp
FEELnc Wucher V 28,053,114 2017 FEELnc (FlExible extraction of LncRNAs), an https://github.com/tderrien/FEELnc
et al. alignment-free program that accurately annotates
lncRNAs based on a random Forest model trained
with general features such as multi k-mer frequencies
and relaxed open reading frames
CPAT Wang L 23,335,781 2013 Coding potential assessment tool (CPAT), which rapidly http://lilab.research.bcm.edu/cpat/
et al. recognizes coding and noncoding transcripts from a
large pool of candidates. To this end, CPAT uses a
logistic regression model built with four sequence
features: Open reading frame size, open reading frame
coverage, Fickett TESTCODE statistic and hexamer
usage bias
CPC Lei Kong 17,631,615 2007 A support vector machine-based classifier, named coding http://cpc.gao-lab.org/
et al. potential calculator (CPC), to assess the protein-
coding potential of a transcript based on six
biologically meaningful sequence features
COME Hu et al. 27,608,726 2017 Using a supervised machine learning model trained on https://github.com/lulab/COME
mRNAs and lncRNAs. It is a robust coding potential
calculation tool for lncRNA characterization based on
multiple features
PLAIDOH Pyfrom 30,767,760 2019 Predicting LncRNA activity through integrative data- https://github.com/sarahpyfrom/
et al. driven ‘omics and heuristics (PLAIDOH). PLAIDOH
PLAIDOH integrates transcriptome, subcellular
localization, enhancer landscape, genome
lncRNAs Functional Prediction Methods and Tools

architecture, chromatin interaction, and


RNA-binding (eCLIP) data and generates statistically
defined output scores
3

(continued)
4

Table 1
(continued)

Methods Authors PMID Year Description URL


ILNCSIM Huang 27,028,993 2016 Improved LRLSLDA by ingrating disease similarity https://www.ncbi.nlm.nih.gov/pmc/
et al. fromLNCSIM and disease Gaussian interaction profile articles/PMC5041953/
kernel similarity
FMLNCSIM Chen et al. 27,322,210 2016 Fuzzy measure-based lncRNA functional similarity https://www.ncbi.nlm.nih.gov/pmc/
calculation model articles/pmid/27322210/
NBCLDA Yu et al. 29,986,541 2018 A novel probability model for LncRNA Disease https://www.ncbi.nlm.nih.gov/pmc/
association prediction based on the Naı̈ve Bayesian articles/PMC6071012/
classifier
Fayaz Seifuddin and Mehdi Pirooznia

PADLMHOOI Xuan et al. 31,191,710 2019 Predicting disease-associated LncRNA-MiRNA pairs https://www.ncbi.nlm.nih.gov/pmc/
based on the higher-order orthogonal iteration articles/PMC6525924/
DCSLDA Zhao et al. 30,046,354 2018 Predicting disease-lncRNA associations based on the https://www.ncbi.nlm.nih.gov/pmc/
distance correlation set and information of the articles/pmid/30046354/
miRNAs
SIMCLDA Lu et al. 29,718,113 2018 Predicting potential lncRNA-disease associations based https://github.com//bioinfomaticsCSU/
on inductive matrix completion SIMCLDA
TPGLDA Ding 29,348,552 2018 lncRNA-disease-gene tripartite graph, which integrates https://github.com/USTC-HIlab/
et. Al. gene-disease associations with lncRNA-disease TPGLDA
associations
PMFILDA Xuan et al. 30,744,078 2019 Infers potential lncRNA-disease associations based on https://www.ncbi.nlm.nih.gov/pmc/
the probability matrix decomposition articles/pmid/30744078/
LLCLPLDA Xie G et al. 31,250,107 2019 Locality-constrained linear coding label propagation https://www.ncbi.nlm.nih.gov/pubmed/
strategy 31250107
BPLLDA Xiao et al. 30,459,803 2018 Based on simple paths with limited lengths in a https://www.ncbi.nlm.nih.gov/pmc/
heterogeneous network articles/PMC6232683/
Lnc2Cancer Gao et al. 30,407,549 2019 Queying experimentally supported long non-coding http://www.bio-bigdata.net/lnc2cancer
RNAs in human cancers
TSSR Ou-Yang 31,191,605 2019 LncRNA-disease association prediction using two-side https://github.com/Oyl-CityU/TSSR
et al. sparse self-representation
ProphTools Navarro C 29,186,475 2017 Based on prioritization tools for heterogeneous https://github.com/cnluzon/prophtools
et al. biological networks
RWLPAP Zhao et al. 30,182,833 2018 Random walk for lncRNA-protein associations https://www.ncbi.nlm.nih.gov/pubmed/
prediction 30182833
LPI-ETSLP Hu et al. 28,702,594 2017 lncRNA-protein interaction prediction using eigenvalue https://www.ncbi.nlm.nih.gov/pubmed/
transformation-based semi-supervised link prediction 28702594
LPI-IBNRA Xie et al. 31,057,602 2019 lncRNA-protein interaction prediction based on https://www.ncbi.nlm.nih.gov/pmc/
improved bipartite network recommender algorithm articles/PMC6482170/
LncRRIsearch Fukunaga 31,191,601 2019 Web server for lncRNA-RNA interaction prediction http://rtools.cbrc.jp/LncRRIsearch/
et al. integrated with tissue-specific expression and
subcellular localization data
LnCompare Carlevaro- 31,147,707 2019 Web server tests for enrichment amongst a panel of http://www.rnanut.net/lncompare/
Fita J quantitative and categorical features
et al.
ACCBN Zhu R 30,626,319 2019 Ant-Colony-clustering-based bipartite network method https://github.com/
et al. for predicting long non-coding RNA-protein BioMedicalBigDataMiningLabWhu/
interactions lncRNA-protein-interaction-prediction
SFPEL-LPI Zhang 30,533,006 2018 Sequence-based feature projection ensemble learning for http://www.bioinfotech.cn/SFPEL-LPI/
et al. predicting LncRNA-protein interactions
lncRNAs Functional Prediction Methods and Tools
5
6 Fayaz Seifuddin and Mehdi Pirooznia

step is to decompose the tripartite network and produce scores of


the lncRNA–miRNA pairs associated with each disease.

2.3 DCSLDA DCSLDA [10] is a novel model based on similarity of disease pairs
and distance correlation to predict potential lncRNA–disease asso-
ciations. It integrates known lncRNA–miRNA associations and
known miRNA–disease associations. In addition, to optimize the
prediction performance of DCSLDA, new methods to calculate the
similarity of disease–disease pairs and lncRNA–lncRNA pairs are
developed simultaneously.

2.4 SIMCLDA SIMCLDA [11] implements lncRNA–disease association as a rec-


ommendation system machine learning problem. Generally, a rec-
ommendation system is an information filtering system that seeks
to predict the preference that user would give to a certain item,
given only partial known preference information. The lncRNA–
disease association prediction task takes the set of lncRNAs, the
set of diseases and the set of partially known associations between
lncRNAs and diseases, then recommends lncRNAs for a given
disease, using prior information about lncRNAs and diseases. Simi-
lar to the assumption in the user-item recommendation system that
users with similar behavior share similar preferences toward items,
the lncRNA–disease prediction assumes that functionally similar
lncRNAs exhibit similar interaction patterns with diseases.

2.5 TPGLDA Tripartite Graph for potential LncRNA–Disease Association iden-


tification (TPGLDA) [12] uses a Tripartite Graph to identify
potential lncRNA–disease associations. It builds a lncRNA–dis-
ease–gene tripartite graph to delineate the heterogeneity of cod-
ing–noncoding genes–disease association. Prediction accuracy is
improved by incorporating lncRNA expression similarity and dis-
ease semantic similarity into the network.

2.6 PMFILDA PMFILDA [13] is a lncRNA–disease prediction model based on


probability matrix decomposition. It constructs three kinds of
binary association networks based on experimentally validated
lncRNA–miRNA associations, miRNA–disease associations, and
lncRNA–disease associations separately. A weighted lncRNA–dis-
ease association network is built using the three individual compo-
nents and updated based on the semantic similarity of disease and
the functional similarity of lncRNA.

2.7 LLCLPLDA LLCLPLDA [14] is based on locality-constrained linear coding


(LLC) to predict lncRNA–disease associations. LLC is leveraged
to project the features of lncRNAs and diseases to local-constraint
features, and then, a label propagation (LP) strategy is used to mix
up the initial association matrix and the obtained features of
lncRNAs and diseases.
lncRNAs Functional Prediction Methods and Tools 7

2.8 BPLLDA BPLLDA [15] infers lncRNA–disease associations by constructing


a network comprising of the known lncRNA–disease association
network, the disease similarity network, and the lncRNA similarity
network. It calculates the lncRNA–disease associations based on the
lengths of the paths connecting them.

2.9 Lnc2Cancer Lnc2Cancer [16] is a systematically curated database that contain


thousands of associations between human lncRNAs and cancer
subtypes curated by reviewing published literature. It contains
associations between lncRNA–miRNA, transcription factors
(TFs), single nucleotide polymorphisms (SNPs), and methylation.
A LncRNA-Cancer_score was developed to evaluate the associa-
tions between lncRNA and cancer.

2.10 TSSR Two-side sparse self-representation (TSSR) model [17] is designed


to learn two nonnegative sparse self-representation matrices which
capture the intrasimilarities among lncRNAs and diseases respec-
tively based on known lncRNA–disease associations. Predictions
can be improved from the intra-associations among disease and
lncRNAs that are derived from external information of lncRNAs
and diseases to generate more accurate estimation of the represen-
tation matrices.

2.11 ProphTools ProphTools [18] is a lncRNA–disease prioritization algorithm. It


performs prioritization on a heterogeneous network combining a
Flow Propagation algorithm similar to a Random Walk with
Restarts and a weighted propagation method.

3 LncRNA–Protein Function Prediction Tools

Tools this category identify the interactions between proteins and


lncRNAs to decipher the functional mechanisms of lncRNAs. A
variety of methods have been developed to predict protein–lncRNA
interactions, among those are, Random Walk for lncRNA–protein
Associations Prediction (RWLPAP) [20], LPI-ETSLP [21] predic-
tion model based eigenvalue transformation, LPI-IBNRA [22]
which uses expression similarity, LncRRISearch [23] interaction
prediction system based on a seed-and-extension approach called
Rlblast [24], LncCompare [25], the Ant-Colony-Clustering-Based
Bipartite Network (ACCBN) [26], and the Sequence-based feature
projection ensemble learning (SFPEL-LPI) [27].

3.1 RWLPAP Random Walk for lncRNA–Protein Associations Prediction


(RWLPAP) [20] is a network algorithm that consists of known
lncRNA–protein interactions, lncRNA sequence similarity matrix,
and protein sequence similarity matrix. Compared to traditional
machine learning methods which require negative samples in the
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8 Fayaz Seifuddin and Mehdi Pirooznia

training data to measure specificity, RWLPAP uses semisupervised


learning strategies to predict unknown data mainly by known asso-
ciations and similarities between them.

3.2 LPI-ETSLP LPI-ETSLP [21] is a link prediction model based on eigenvalue


transformation to predict lncRNA–protein interactions. It inte-
grates known lncRNA–protein association, lncRNA–lncRNA simi-
larity network and protein–protein similarity network to predict
potential lncRNA–protein interactions. It is also based on the
similarity matrix rather than data features and thus does not require
negative samples in the training data to assess the specificity.

3.3 LPI-IBNRA LPI-IBNRA [22] uses known lncRNA–protein and protein–pro-


tein interactions, and lncRNA expression similarity, and then elim-
inates second-order correlations on the bipartite network
appropriately to enhance the prediction accuracy.

3.4 LncRRIsearch LncRRIsearch [23] is a web server for comprehensive prediction of


human and mouse lncRNA–mRNA and lncRNA–lncRNA interac-
tions. Utilizing the human and mouse transcriptome in an ultrafast
RNA–RNA interaction prediction system based on a seed-and-
extension approach called Rlblast [24], it provides multiple local
base-pairing interactions for each lncRNA–RNA interaction. It
integrates tissue-specific RNA expression and subcellular localiza-
tion data of lncRNAs which help to strengthen the accuracy of the
predicted interactions.

3.5 LnCompare LnCompare [25] is a tool that compares lncRNA genes based on a
comprehensive feature set with more than 100 attributes covering
diverse aspects, including gene structure, nucleotide composition,
evolutionary conservation, cell and tissue expression, subcellular
localization, tissue specificity, repetitive sequence content, and phe-
notypic association. It is comprised of two main modules: (1) gene
set feature comparison which compares two sets of lncRNAs, and
identifies significantly different features, both categorical and quan-
titative; (2) similar gene discovery which uses user-defined gene(s)-
of-interest to query for the set of most similar lncRNAs, based on
one or more features.

3.6 ACCBN The Ant-Colony-Clustering-Based Bipartite Network (ACCBN)


[26] method predicts lncRNA–protein interactions using three
techniques: (1) lncRNA is represented as a feature vector and
lncRNA is used as a data point in the feature space; (2) the similarity
is enhanced by using the Ant Colony Clustering method and
(3) effective prediction of lncRNA–protein interactions is achieved
by applying a lncRNA–protein bipartite network.
lncRNAs Functional Prediction Methods and Tools 9

3.7 SFPEL-LPI Sequence-based feature projection ensemble learning (SFPEL-


LPI) [27] method predicts lncRNA–protein interactions using
two approaches: (1) extracts lncRNA sequence-based features and
protein sequence-based features; (2) calculates multiple lncRNA–
lncRNA similarities and protein–protein similarities by using
lncRNA sequences, protein sequences, and known lncRNA–pro-
tein interactions. Then, it combines multiple similarities and multi-
ple features with a feature projection ensemble learning frame.

4 LncRNA Coding potential Calculators

In recent years machine learning methods have become a great asset


to assess the protein-coding potential of lncRNAs using supervised
machine learning model trained on mRNAs based on features
curated from sequence information, such as open reading frame
(ORF) length and coverage, nucleotide composition features,
k-mer sequence motif and codon usage, conservation scores, and
secondary structure.

4.1 Sc-ncDNAPred Sc-ncDNAPred [28] uses a support vector machine (SVM)-based


computational algorithm to classify noncoding RNA(ncDNA)
sequences in Saccharomyces cerevisiae (S. cerevisiae). Several features
such as mononucleotide composition (MNC), dimer nucleotide
composition (DNC), trimer nucleotide composition (TNC), tetra-
mer nucleotide composition (TrNC), pentamer nucleotide compo-
sition (PNC), and hexamer nucleotide composition (HNC) are
used to identify noncoding RNA.

4.2 FEELnc FlExible Extraction of LncRNAs (FEELnc) [29] is a tool developed


to annotate lncRNAs from RNA-seq assembled transcripts. It clas-
sifies/annotates and calculates the coding potential of lncRNAs.
FEELnc annotates lncRNAs based on a machine learning method,
Random Forest (RF), trained with general features such as multi k-
mer frequencies, RNA sequence length and open reading frames
(ORFs) size. It is comprised of three modules: (1) filter, (2) coding
potential, and (3) classifier.

4.3 CPAT Coding-Potential Assessment Tool (CPAT) [30], an alignment-


free program, which uses logistic regression to distinguish between
coding and noncoding transcripts on the basis of four sequence
features.

4.4 CPC Coding Potential Calculator (CPC) [31] is a support vector


machine (SVM)-based classifier developed to assess the protein-
coding potential of a transcript based on six biologically meaningful
sequence features.
10 Fayaz Seifuddin and Mehdi Pirooznia

4.5 COME Come [32] (coding potential calculator based on multiple evi-
dences), is using a supervised machine learning model trained on
mRNAs and lncRNAs. It is a robust coding potential calculation
tool for lncRNA characterization based on multiple features. It
integrates multiple sequence-derived and experiment-based fea-
tures using a decompose–compose method and substantially
improves the consistency of predication results from other coding
potential calculators.

5 Hybrid Tools

Hybrid methods combine multiple algorithms and features in order


to capture complex correlations at multiple levels. ILNCSIM [33],
FMLNCSIM [34], and PLAIDOH [35] are among them, and they
all use a combination of features and multiple methods in order to
achieve better performance and higher accuracy. Integration multi-
ple features and approaches will likely reduce technical noise and
may depict true mechanisms of lncRNA function.

5.1 ILNCSIM Improved LNCRNA functional SIMilarity calculation model


(ILNCSIM) [33] is a lncRNA–disease association predictor that
integrates known lncRNA–disease associations and disease
Directed Acyclic Graphs (DAGs) and calculates diseases similarity
by an edge-based calculation model. It computes the functional
similarity of two lncRNAs based on the semantic similarity of
disease groups associated with these two lncRNAs. To further
evaluate the performance of ILNCSIM, the calculated lncRNA
functional similarity was used to predict the lncRNA–disease asso-
ciations by combing ILNCSIM with the model of LRLSLDA [36].

5.2 FMLNCSIM Fuzzy Measure–based LNCRNA functional SIMilarity calculation


model (FMLNCSIM) [34] was designed on the basis that similar
diseases tend to be involved with functionally similar lncRNAs and
vice versa. The first step involves grouping diseases with similar
descriptions/terms together computed by combining the concepts
of information content and fuzzy measure. The second step
involves computing functional similarity of two lncRNAs based
on the semantic similarities of their associated disease groups. To
further evaluate the performance of FMLNCSIM, the calculated
lncRNA functional similarity was used to predict the lncRNA–
disease associations by combing FMLNCSIM with the model of
LRLSLDA [36].

5.3 PLAIDOH Predicting LncRNA Activity through Integrative Data-driven


‘Omics and Heuristics (PLAIDOH) [35] is a recently developed
computational method that integrates multiomics data to rank
functional connections between individual lncRNA, coding gene,
lncRNAs Functional Prediction Methods and Tools 11

and protein pairs. It combines transcriptome, subcellular localiza-


tion, enhancer landscape, genome architecture, chromatin interac-
tion, and RNA-binding data, generating statistically defined output
scores for ranking lncRNAs.

6 Conclusion

lncRNAs are described as “Dark Matters” of our genome


[37]. However, advances in NGS technology in recent years iden-
tified functionality of thousands of as abnormally altered in the
cancer genome, differentially expressed in different tissues or con-
ditions, or aberrant biological processes. However, despite many
challenges, the therapeutic potential of lncRNAs have attracted
considerable interest in the past few years. The experimental tech-
nologies and approaches to uncover the function of lncRNAs are
promising but remain expensive and limited currently. Computa-
tional frameworks for predicting lncRNA function have greatly
advanced in recent years. While they are extremely useful to
uncover the lncRNAs function, the staggering complexity of the
lncRNA transcriptome, in many cases remains challenging and
requires further investigations [38]. Here, we systematically
reviewed various computational algorithms and prediction tools
that have been developed to elucidate the roles of lncRNAs. We
hope this review will assist researchers and scientists in understand-
ing methodologies for deciphering lncRNAs functionalities as well
as provide suggestions for new directions in future development.

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street, Unthank’s road
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Life office, Surrey street
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Advertisement, p. 10)
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Miles’
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Easto, George, Church Style, Upper Market
Eastoe, Mr. Robert, New road, Town close
Easton, Haylett, beer retailer, Magdalen street
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Easton, Isaac, fishmonger, St. James’ street
Eaton, Mr. Thomas D., Chapel field
Edgar, Mrs. Elizabeth, 2, Grove place, St. Giles’ road
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Edwards, Benjamin, city missionary, Trory street, Unthank’s road
Edwards, Charles, Earl of Leicester, Brazen Doors road
Edwards, Edward Manning, haircutter and perfumer, 40, London
street
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Edwards, Miss Mary Ann, St. Stephen’s road
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Ellingham, Henry, plumber, glazier, and painter, Elm hill
Elliott, Mr. John, 2, The Crescent
Elliott, Miss Mary, milliner, Bank street
Ellis, Benjamin, the Dove tavern, Lower Westwick street
Ellis, John, joiner and builder, Oak street, St. Martin’s
Ellis, John, land agent and surveyor, Bank plain
Ellis, Mary, green grocer, St. Mary’s
Ellis, Mrs. Mary, All Saints’ green
Ellis, Mrs. Priscilla, lodging-house keeper, 15, and 16, Chapel Field
Ellis, Rev. Robert Stanton, Wesleyan minister, Calvert street
Ellis, Samuel, beer retailer, Oak street, St. Martin’s
Ellis, Thomas, green grocer, Cubitt’s court, Bethel street
Ellis, Thomas Richard, The Wilderness, Bracondale
Ellis, William, green grocer, Oak street
Ellis, William, green grocer, Bridge street, St. Miles’
Ellison, Mrs. Francis, barometer and thermometer maker, and
fancy repository, Dove street
Ellison, Robert, wood turner, Upper Goat lane
Ellison, William, beer retailer, King street gates
Elmer, Mrs. Ann, Chapel Field grove
Elmer, Edmund, merchant’s clerk, Hall road, Lakenham
Elmer, John, market gardener, Lower close
Elmer, John, accountant, St. Catherine’s plain
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Empson, Ezra, baker, St. James’ street
Emslie, James and Son, engravers, chromo-lithographers,
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Engall, Joseph, game dealer, St. Augustine’s street
Engall, Thomas, Fleckered Bull, Ber st.
England, William, coal merchant, St. Ann’s terrace, Synagogue
street
English and Son, drapers and silk mercers, London street
English, John, (see English and Son); h 1, London terrace, St.
Stephen’s road
English, Joseph, woollen draper and tailor, 45, London street
English, Joseph, chemist and druggist, St. Giles’ street
English, Mr. Richard, Holl’s lane
English, Mrs. Sarah, Albion House, Market place
English, William, (see English and Son) h 1, Lakenham terrace,
city road
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agent, Distillery street
Etheridge, Mrs. Elizabeth, Thorpe hamlet
Etheridge, George and William Ellis, watch and clock makers,
goldsmiths, silversmiths, and jewellers, 10, The Walk
Etheridge, Thomas William, Carrow road, Thorpe hamlet
Evans, Bernard, solicitor’s clerk, Lower close
Evans, Charles, counsellor, King street
Evans, Rev. Edward, B.A. (vicar of St. Stephen’s) Surrey street
Evans, George, shopkeeper, Barrack street, Pockthorpe
Evans, Misses Lucy and Emma, dressmakers, Lower close
Evans, Mrs. Lacy, Upper Surrey street
Everard, John, commercial traveller, 10, Bedford street, Unthank’s
road
Everett, James, drill-master, Coldstream terrace, Bedford street,
Unthank’s road
Everett, John, wool warehouse, Thorpe hamlet
Everett, Joseph, wool stapler, Bishopgate street
Everett, Mr. Robert, Mount Pleasant, Newmarket road
Everett, Thomas, merchant, Trory street, Unthank’s road
Everett, William Wilson, tailor and hatter, Red Lion street
Everitt, Miss Ann, Prince’s street
Ewing, John William, nurseryman, seedsman, and florist, and lime
burner, Exchange street, and Eaton
Ewing, Mr. William Charles, Post Office street
Fabb, Sarah, Nelson street, Heigham fields
Fair, Thomas, general shopkeeper, Bishopgate street
Fairchild, Mary Ann, linen draper, Spitalfields, Thorpe hamlet
Fairhead, Maria, upholsteress, West Pottergate street
Fairhead, Louisa, dealer in British wines, milliner and dress maker,
Pottergate street
Fairman, Thomas, builder, 5, Oxford street, Unthank’s road
Fairman, William, hairdresser, Barrack street, Pockthorpe
Fairweather, Mrs. Lydia, linen-draper, silk mercer, hosier, and
haberdasher, London street
Fake, John, the Wrestlers, St. James’ street
Farman, George, general dealer, Blazeby’s buildings, Scole’s green
Farmer, Benjamin, British school-master, Colegate street
Farnell, James Thomas, boarding and day school, Tuck’s court, St.
Giles’ street
Farnell, William Keeling, classical and mathematical boarding
school, Theatre-street house school
Farrow Maria, corset and stay maker, Grapes’ hill, St. Giles’
Farrow, Thomas, general shopkeeper, Chapel street, Union place
Farrow, Thomas, market gardener, Newmarket road
Farrow, William, Scripture reader, Oak street
Faulke Robert, baker, Queen street, Crook’s place
Fawcett, Mr. Samuel, Mousehold, Thorpe hamlet
Fearnside, Benjamin, furniture broker, Coach and Horses, Red Lion
street
Featherstone, Thomas, accountant, Distillery street
Feek, William, horse breaker, West Pottergate street
Felstead, Miss Charlotte, straw bonnet maker and furrier, 20,
Castle meadow
Felstead, James, grocer, Regent street, Union place
Felstead, Robert, Catherine Wheel, St. Augustine’s
Feltham, Barnabas, miller, New Lakenham
Feltham, Charles, ferry boat owner, Lower close
Fenn, James, French polisher, Cogman’s yard, Ber street
Fenn, John, merchant’s clerk, 5, Langham place, Dereham road
Fenn, Mrs., stay maker, Julian street
Fenn, Mrs., St. Giles’ terrace, Bethel street
Fenn, Robert, grocer and tea-dealer, Magdalen street
Fenn, Thomas, boot and shoe maker, 35, Pottergate street
Fenn, Thomas, Hen and Chickens, St. Mary’s plain
Ferra, John, hairdresser, King street
Ferron, Mrs. Ellen Jane, Unthank’s road
Fickling, Harriet, stationer and haberdasher, Kensington place, St.
Catherine’s plain
Fickling Robert, solicitor, Prince’s street
Fiddament, James, green grocer, Ber street
Fidgett, Miss Henrietta, 38, Victoria street, St. Stephen’s
Field and Bignold, solicitors, Upper Surrey street
Field, Edward, (see Field and Bignold) Surrey street
Field, Robert, King street
Field, William C., commercial traveller, Brunswick road, Newmarket
road
Fife, James, Inland Revenue officer, Baxter’s gardens, King street
Figg, George, Boar’s Head Inn, Surrey street
Finch, James, chimney sweeper, St. Miles’ church alley
Finch, John, carpenter, Trowse
Finch, Walter, locksmith, Elm hill
Finch, William, horse-hair seating and crinoline manufacturer,
Prince Regent, Weaver’s lane
Finch, William, chimney sweeper, St. Miles’ church street
Finch, William H., blacksmith, Wagon and Horses lane, Tombland
Finegan, Mrs. Ann, ladies’ school, Cow hill
Finegan, Thomas William, linguist, Cow hill
Firth, George Warren Watts, surgeon, registrar of births and
deaths for the Wymer district, 66, St. Giles’ street
Fish, John, shoemaker, Grout’s thoroughfare, Timberhill street
Fish, Mrs. Lucy, shirt maker, 51, Pottergate street
Fish, Thomas, hosier, glover, and shirt maker, Orford hill
Fish, Thomas, boot and shoe maker, 51, Pottergate street
Fish, William, professor of music, Bedford street, St. Andrew’s
Fisher, Daniel, school-master, 6, Lakenham terrace, City road,
Lakenham
Fisher, Edward, butcher, Fisher’s yard, Ber street
Fisher, Mrs. Elizabeth, 4, Lame Dog road
Fisher, Francis, boot and shoe maker, Chapel street, Crook’s place
Fisher, George, last maker, Union place
Fisher, James, solicitor, Lower close, (see Steward and Fisher)
Fisher, James, boat builder, Oak street
Fisher, James Cracknell, grocer and tea-dealer, 62, St. Stephen’s
street
Fisher, Joseph, boot and shoe maker, Lower King street
Fisher, Mary Ann, butcher, Distillery street, Heigham
Fisher, Robert, grocer and tea-dealer, Bridge street, St. George’s
Fisher, Robert, grocer and tea dealer, Sussex street
Fisher, Mrs. Sarah, shopkeeper, Oak street
Fisher, Thomas, joiner and builder, Museum court, St. Andrew’s; h
Crescent, Chapel field
Fisher, William, carpenter, St. Paul’s terrace, Cowgate street
Fishwick, Rev. John, Catholic priest, Catholic chapel, Willow lane
Fisk, Adam, Phœnix brewery, Magdalen street
Fiske, Francis Robert, draper, silk mercer, &c., London street
Fisk, Mrs. Mary Margaret, The Chantry
Fiske, Mrs. Harriet, 3, Foundry terrace, Thorpe hamlet
Fitch and Chambers, dispensing and family chemists, Market place
Fitch, Charles, grocer and tea dealer, Coslany street, St. Miles’
Fitch, Robert, chemist and druggist, (see Fitch and Chambers)
Market place
Fitt, Edward, beer retailer, Duke of Wellington, Wellington street
Fitt, Eliza, The Gin Shop, Castle meadow
Fitt, Mr. George, Town close, Newmarket road
Fitt, James, butcher, Ber street
Fitt, Miss Jane, Cowgate street
Fitt, John Mason, baker, Coburg street
Fitt, John, green grocer, Botolph street
Fitt, Nathaniel, tobacco-pipe maker, Cherry street, Lakenham
Fitt, Richard, farmer, Earlham road
Fitt, Robert, tobacco-pipe maker, Ber street
Fitt, William, butcher, Ber street
Fitzgerald, Abraham, coal dealer, Cowgate street
Fitzgerald, Charles, musician, Rose lane
Fitzgerald, Louisa, dressmaker, Cowgate street
Flatt, John, ironmonger, Magdalen st.
Flatt, William, ironmonger, 52, St. Stephen’s street
Flaxman, Martha, Richmond terrace, Bracondale
Fleet, James Robert, commercial traveller, Dereham road
Fletcher, Josiah, printer, publisher, bookseller, binder, and
wholesale stationer, and agent for the National Mercantile Life
Assurance, 8, The Walk; h Unthank’s road
Fletcher, Joseph, Red Lion, Bridge street, St. Andrew’s
Fletcher, Sarah, furrier, Finket street
Flood, Francis, shopkeeper, St. Martin’s lane
Flood, Harriet, draper, St. Benedict’s st.
Flower, Jonathan, wholesale draper, Wensum street
Flowerdew, Richard J., auctioneer, (see Clowes and Flowerdew); h
Heigham grove, St. Giles’ road
Foley, Mrs. Susan, milliner, &c., Union place
Folk, Charles, baker, St. Augustine’s street
Folk, Charles, butcher, Gildengate street
Folkard, George, green grocer, Oak street, St. Martin’s
Ford, Miss Ann, straw bonnet and dress maker, Wellington lane,
St. Giles’
Ford, Elizabeth, milliner, Pitt street
Ford, John, gardener, Pitt street
Ford, Mrs., 9, St. Stephen’s square
Ford, Robert, carpenter and builder, St. George’s plain; h St.
Helen’s cottages, Thorpe hamlet
Ford, William, and Son, wholesale boot and shoe manufacturers,
Colegate street
Ford, William F., (see Ford, William and Son); h Earlham road
Forder, James, blacksmith, Chapel Field road
Forrester, Mr. George, Tombland
Forster, Edward, umbrella maker, Chapel Field road
Forster, John, umbrella, parasol, and straw hat manufacturer, 28,
London street
Forster, Samuel, grocer and provision dealer, Pockthorpe
Forster, Thomas, grocer, &c., Queen street, Crook’s place
Foster, Francis Gostling, solicitor, St. Giles’ road
Foster, George, Norfolk Commercial Inn, family hotel and posting
house, and omnibus and fly proprietor, St. Giles’ street
Foster, John, shopkeeper, Wellington street
Foster, Joseph, tea dealer, Sussex street
Foster, Samuel, 11, Nelson terrace, Grove road, New Lakenham
Foster, Thomas, general shopkeeper, West Pottergate street
Foster, (Sir William) Sons, Burroughes, and Robberds, solicitors,
Crown Bank plain
Foster, Sir William, bart., 54, St. Giles’ street
Foulger, Horatio, builder and shop-keeper, Chapel Field road
Foulger, Robert, gig maker, Ber street
Foulger, Rev. William, Upper King street
Foulsham, Francis, draper, Bedford street, St. Andrew’s
Foulsham, Henry, leather merchant, Magdalen street
Foulsham, Mrs. Susan, Lame Dog road
Foulsham, Thomas, auctioneer and appraiser, &c., Westlegate
street, (see Advertisement, p. 28)
Foulsham, Thomas, Lame Dog road
Foulsham, William, tobacconist, Orford hill
Fountain, Elizabeth, shopkeeper, Heigham street
Fountain, Mrs. Mary Ann, dining and luncheon rooms, London
street
Fountain, Mary Ann, beer retailer, King street
Fountain, Thomas, accountant, Seymour place, St. Stephen’s
square
Fox, Edward and William, Mousehold, Thorpe hamlet
Fox, Frederick, solicitor, Surrey court, Surrey street
Fox, George Washington, accountant, St. Leonard’s hill, Thorpe
hamlet
Fox, Henry, tailor, Dereham road
Fox, Henry, Lime Kiln inn, Trowse
Fox, Isaac, The Queen’s Head, Upper St. Giles’
Fox, James, Little John, Alms’ street, Heigham
Fox, Joel, wholesale and retail fur manufacturer, 11, The Walk
Fox, John, surgeon, Upper St. Giles’ street
Fox, John, carpenter and builder, Heigham causeway
Fox, Maria, tailoress, Tinkler’s lane
Fox, Mrs. Mary, baker, Lower Close
Fox, Mr. Samuel Henry, St. Stephen’s gates
Fox, Thomas, carpenter and contractor, Heigham street
Fox, Thomas Colman, solicitor, 22, Victoria street, St. Stephen’s
road
Fox, William, baker, Cowgate street, St. Paul’s
Fox, Mr. William, Lame Dog road
Fox, William, shoemaker, Russell street
Foyson, Robert, Pump street
Foyson, Robert B., builder, (see Minns and Foyson); h Pump street
Foyson, William, commercial traveller, Green Hills, Aylsham road
Francis, W. Bransby, surgeon, registrar of births and deaths for the
Coslany district, Colegate street
Francis, George, general shopkeeper, Trafalgar street, Lakenham
Francis, Henry Clark, station master, Thorpe station; h Rose lane
Francis, Joseph, general clothier, Bridge street, St. Miles’
Francis, Thomas, estate agent, Newmarket road
Francis, Thomas, green grocer, Timberhill street
Franklin, Mr. Charles, All Saints’ green
Franklin, Charles, wheelwright and blacksmith, Cardigan street,
Heigham
Frary, Richard, piece broker, St. Andrews’ hill
Frary, Valentine William, watch and clock maker, Back of the Inns
Fraser, James Edward, solicitor, Bank chambers, Bank place, and
Wisbeach, Cambridgeshire; h St. Giles’ road
Fraser, John, linen draper, Dereham road
Fraser, William, woollen cloth and Manchester warehouse man,
Exchange street; h Ipswich, Suffolk
Frazer, Charles, saw mills, (see Saul and Frazer); h Golden Ball
lane
Freeman, Mrs. Ann, Earlham road
Freeman, Charles J., cabinet manufacturer, London street; h
Bracondale, (see Freeman and Wells)
Freeman, Charles Robert, corn and flour cellar, Upper Market; h
Eaton
Freeman, Edward, wholesale shoe manufacturer, St. Martin’s lane,
St. Martin’s at Oak
Freeman, James, baker, 15, St. Giles’ street
Freeman, Mr. James, Holl’s lane, Heigham fields
Freeman, James, jun., professor of music, Caledonia terrace,
Dereham road
Freeman, Mr. James, Caledonia terrace, Dereham road
Freeman, Jeremiah, blacksmith, Barn road
Freeman, John, bricklayer and builder, Nelson street, Heigham
Freeman and Nash, cheese factors, wholesale grocers and tallow
chandlers, Upper market
Freeman, Richard, boot and shoe maker, Upper Westwick street
Freeman, Samuel, beer retailer, Quay side
Freeman and Wells, upholsterers, decorators, and undertakers,
cabinet and chair manufacturers, 37, London street
Freeman, William, carver and gilder and artist, St. Benedict’s plain,
Pottergate street
Freeman, William, baker and shopkeeper, Chapel street, Union
place
Freeman, William, jun., carver, gilder, and photographic artist,
Rampant horse street
Freestone, Anthony, baker, Fye bridge
Freestone, Edward, solicitor, Little Orford street
Freestone, Robert, merchant’s clerk, Oxford street, Unthank’s road
Freestone, Samuel, baker, Old Church road, New Lakenham
Freestone, William, Wellington Tavern, Muspole street
French, Robert, (see Kitton, French and Co.); h Tombland
French, Robert, tailor, Tabernacle street
Froggett, Ellen, boarding school, Sussex street
Frohawk, Nicholas, Priest’s buildings, St. Stephen’s road
Fromow, John, clothier, Lower Westwick street
Fromow, Stephen, cattle salesman, 5, Grove place, Surrey road
Frost, Charles, builder and carpenter, Chapel Field road
Frost, George, accountant, St. Faith’s terrace, St. Faith’s lane
Frost, Hezekiah, market gardener, Lower close
Frost, Mrs. Mary, portmanteau, trunk, and carpet bag
manufacturer, and stay and corset maker, 15, Davey place
Frost, Mary Ann, shopkeeper, Magdalen street
Frost, Samuel Johnson, agent to the Friend in Need Life and Sick
Insurance Compy., Howard street, Grove place, Lakenham
Frost and Son, carpenters, builders, and cabinet makers, 7, Chapel
Field road
Frost, Thomas, tallow chandler, Fishgate street
Frost, Rev. William, B.A., Thorpe lodge
Frost, William, coffee and eating house, 2, Upper Walk
Fryer, William, sawyer, Union place
Fryer, William, wholesale boot and shoe manufacturer, Ber street;
h Union place
Fulcher, Christmas, watch and clock maker, Mousehold, Thorpe
hamlet
Fulcher, Mr. James, Chapel street, Crook’s place
Fulcher, William, millwright, millstone builder, &c., Mousehold
heath (see Advertisement, p. 34)
Fuller, Benjamin, commercial traveller, 37, Victoria street, St.
Stephen’s
Fuller, E., dressmaker, Pitt street
Fuller, Edward, tailor, Red Lion street, St. Stephen’s
Fuller, Henry Nicholas, musician, Trafalgar street
Fuller, James, saddler and harness maker, 23, Old Haymarket
Fuller, John, shoemaker, Quay side
Fuller, John, jobbing gardener, Thorpe hamlet
Fuller, Maria, midwife, Ber street
Fuller, Robert, The Trumpet, St. Stephen’s street
Fuller, Thomas Benjamin, printer, bookseller, and stationer, St.
Stephen’s street
Fuller, William, tobacconist and news’ agent, Red Lion street
Fuller, William H., confectioner, Theatre street; h Red Lion street
Furse, James Thomas, cabinet maker and upholsterer, Prince’s
street
Furse, Mrs. Maria, dyer, St. Augustine’s street
Furse, William, dyer and scourer, Peacock street
Furze, Robert, green grocer, Heigham street
Fussey, Susan, butcher, Ber street
Gadge, Sarah, St. Miles’ Coslany
Gaffer, Samuel, Paul Pry hill, Heigham
Gallant, George, Mousehold saw mills, Thorpe hamlet
Gandy, George, merchant’s clerk, Thorpe hamlet
Ganly, James, designer for embroidery, trimming, wool, and fancy
repository, London street (see Advertisement, p. 34)
Gardiner, Charles, waiter, Rose lane
Gardiner, Maria, green grocer, Upper Westwick street, St. Swithin’s
Gardiner, William, chemist and druggist, Dove street
Gardiner, William, Red Lion, London street
Gardiner, William, rag merchant, St. Paul’s street
Gardner, Maria, pork butcher, Barn road
Gardner, Thompson, boot and shoe maker, Mount Pleasant
Garner, Mrs. Sarah, tailoress, Gildengate street
Garnham, William, grocer, and clerk of St. Mark’s church, Hall
road, New Lakenham
Garrett, John, draper, Pottergate street
Garrod, Edward, editor of the “Norfolk Chronicle,” Private Road
villas, Unthank’s road
Garrod, Mrs. Mary Sophia, Thorpe hamlet
Garthon, James Slapp, surgeon, Upper St. Giles’ street
Garwood, Mrs. Sarah Ann, St. Clement’s hill, New Catton
Gaul, Edward John, shuttle maker, Magdalen street
Gaul, Mrs. Maria, Prince’s street
Gay and Co., brush, basket, sieve, mat, and matting
manufacturers, Upper Market
Gay, Edward, shopkeeper, Heigham street
Gay, James, shoemaker, City road, Heigham fields
Gay, Samuel, green grocer, Bridge street, St. Miles’
Gayford, William George, station master, Trowse station
Gaze, George, timber merchant, Grapes’ hill, St. Giles’
Gaze, James, shoemaker, Playford’s court, Pottergate street
Gaze, Matthew, carpenter and builder, King street
Gaze, Richard, clerk, Golding street, St. Benedict’s road
Gaze, Samuel, hairdresser, Lower Westwick street
Gaze, Susan, 63, St. Giles’ street
Gaze, William, engineer, Pitt street
Gaze, William, merchant’s clerk, Lower Close
Gaze, William Hammond, register office for servants, Wrestlegate
street
Gaze, William, millwright and engineer, St. Paul’s Back lane
Gazeley, James, green grocer, Lower Westwick street, St.
Margaret’s
Gearing, James, The Bee Hive, St. Stephen’s gates
Geary, William, manufacturer, Gildengate street
Gedge, Edward Peter, shopkeeper, Brazen Doors road
Gedge, Frederick, Caledonia terrace, Dereham road
Gedge, George, dyer, finisher, and hot-presser, Coslany street
Gedge, Robert, plumber, Wounded Hart lane
Gedge, Robert, shoemaker, Ber street
Gedge, William, baker, Chapel street, Union place
Gedge, William, hairdresser, Upper Westwick street
Geldart and Son, wine merchants, Wensum street
Geldart, Herbert D., Esq., Thorpe hamlet
Geldart, Robert, Esq., Thorpe hamlet
Gent, David, St. John’s Head, Coslany street
Gent, Eliza, straw bonnet maker, Muspole street
Gent, George, boot and shoe maker, Coslany street
Gent, George, shopkeeper, Bridge street, St. Miles’
Gent, Thomas William, merchant’s clerk, Dereham road
George, John, tailor, Muspole street, St. Mary’s
George, Michael Richard Dunn, coal merchant, Quay side
George, Robert Mills, bricklayer and plasterer, and shopkeeper, St.
Benedict’s street
George, Robert, fish merchant, St. Benedict’s street
George, Robert, builder, Muspole street
George, William Morris, carpenter and builder, Pottergate street
Gerard, William Sinclair, jeweller, dealer in coins and medals, and
hairdresser, Botolph street
Gibbs, Richard, The Rose and Crown, Bishopgate street
Gibbs, Rudd William, butcher, Palace street
Gibbs, William, glass and china mender, Meadows’ yard, Coslany
street
Gibson, Alfred, general shopkeeper, Botolph street
Gibson and Bateman, surgeons, 19, St. Giles’ street
Gibson, Charles M., Bethel street (see Gibson and Bateman)
Gibson, George, The White Horse, Crook’s place
Gibson, The Misses, Lower Close
Gibson, Mr. Isaac, Upper Heigham
Gibson, John, boot and shoe maker, and tobacconist, Pitt street
Gibson, Robert, leather merchant and shoe manufacturer, St.
Stephen’s street
Gibson, Mrs. Rosamond, Mount Pleasant, Newmarket road
Gibson, Samuel, butcher, Gildengate street
Gibson, William, baker, St. Catherine’s plain
Gibson, William, (see Copestake and Co.) commercial traveller, The
Chantry
Giddens, Miss Susanna, circulating library, St. Stephen’s street
Gidney, Frederick, Hospital school, Fishgate street
Gidney, Robert, watch and clock maker, Orford hill
Gidney, Samuel, The Bushel, St. Augustine’s
Gilford, Samuel, general shopkeeper, St. Benedict’s street
Gifford, Thomas, tailor, Magdalen street
Gilbeigh, Mrs. Caroline, Spread Eagle tavern, Old Haymarket
Gilbert, George, coachsmith, patent axle-tree and spring maker,
Timberhill street
Gilbert, Mrs., day school, Gildengate street
Gilbert, Samuel James, plumber, painter, and glazier, Grapes’ hill
Gilbert, William, builder, St. Augustine’s
Gill, James, baker and grocer, Lower Westwick street
Gill, John, earthenware dealer, St. Giles’ street
Gilham, Miss Judith, West Pottergate street
Gilman, Charles Rackham, solicitor, secretary to the Norfolk
Farmers’ Cattle Insurance Society, and agent to the City of
Glasgow Life Insurance Compy., St. Giles’ street; h Unthank’s
road
Gilman, Charles Suckling, solicitor and share broker, secretary to
the General Hail Storm Insurance Society, secretary to the
Chamber of Commerce, and manager of the Norwich and
London Accident and Casualty Insurance Association, St. Giles’
street
Gilman, John, carver and gilder, publisher and printseller, gallery of
fine arts, 26, London street
Gipson, James, carter, Mousehold
Gipson, Samuel, carter, Mousehold
Girdlestone, Reuben, hair dresser, branch post office, 8, Upper St.
Giles’ street
Girdlestone, Thomas, Three Horse-shoes, Palace street
Girling, Elizabeth, baker, (opposite the church) New Catton
Girling, Miss Maria, Kimberley street, Unthank’s road
Girling, Robert, butcher, St. Benedict’s street
Girling, Sherwood, grocer, Lower Westwick street
Girling, William, Golden Ball inn, hay, corn, and straw merchant,
Golden Ball street
Glasspoole, Mr. George, Rose valley, Unthank’s road
Glendenning, John Brown, (see Colman and Glendenning); h St.
Stephen’s road
Goading, William, milliner, Red Lion street
Goat, Charles, The Old Goat inn, Upper Goat lane
Godbold, Henry, clerk, Paragon street
Goddard, Thomas, Black Prince, Upper Walk
Godfery, Elizabeth, dressmaker, Duke st.
Goffin, Mrs. Mary, dressmaker, &c., Golden Dog lane
Goffin, Mrs. Matilda Elizabeth, boot and shoe warehouse, Palace
street
Goggs, Matthew, Esq., Curfew cottage, Earlham road
Goggs, William, grocer, tea and coffee dealer, foreign fruit, British
wine, and provision merchant, St. Giles’ gates
Gold, James Charles, news’ agent, Baker’s road, St. Augustine’s
Golden, William, coal dealer, Twiddy’s court, Ber street
Golder, Edward, grocer, Oak street
Golder, Mrs. Hester, toy dealer, Upper Westwick street
Golding, John, Cellar House, Bridge street, St. George’s
Golding, Mary Ann, day school, St. Paul’s Back lane
Goldsmith, Charles, grocer, &c., Surrey street
Goldsmith, James, grocer and tea dealer, 34, St. Stephen’s street
Goldsmith, James, boot and shoe maker, Back of the Inns
Goldsmith, Mary, tailoress, Upper King street
Goldsmith, Sarah, tailoress, Duke street
Goldsmith, Thomas, corn merchant and confectioner, St. Stephen’s
Goldspring, Mary Ann, dressmaker, William street
Gooch, Mrs. Amelia, Newmarket road
Gooch, George Carver, water-closet manufacturer, and plumber,
glazier, and painter, Castle meadow and King street (see
Advertisement, p. 21)
Gooch, Henry, harness maker, St. James’ street
Gooch, Joshua, fringe, lace, and damask warehouse, 3, Dove
street
Gooch, Henry, Brewery Cottage, King street
Gooch, Noah, Malt and Hop tavern, Charing cross
Gooch, Mrs. Phœbe, milliner and dressmaker, Waddington’s
terrace, Thorn lane
Gooch, Robert, secondhand bookseller, White Lion street
Gooch, Samuel Irwin, currier and leather seller, 9, Davey place
Gooch, Thomas, brush manufacturer, 7, Grout’s thoroughfare
Gooch, Thomas Henry, Royal Hotel tap, Back of the Inns
Gooch, William, Unthank’s road
Good, Thomas, boot, shoe, and last maker, Bridge street, St.
George’s
Gooderham, Samuel, tunist, &c., Elm hill
Gooderson, Mr. John, West Pottergate street
Gooderson and Moll, linen and woollen drapers, Upper Market
Gooding, Mrs. Harriet, straw bonnet maker, Red Lion street
Goodson, Mr. Robert, Alms’ lane, St. George’s
Goodson, William, butcher, Dereham rd.
Goodwin, Charles, surgeon, Willow lane
Goodwin, John, solicitor, Willow lane; h Thorpe hamlet
Goodwin, Mrs., Willow lane
Goodwin, Rev. William, M.A., incumbent of St. Benedict’s, 14,
Chapel field
Gooke, David, shoemaker, Rose lane
Goose, Agas, solicitor’s clerk, Theatre street
Goose, Mrs. Emma, milliner, 15, Briggs’ street
Goose, Jacob, green grocer, Golden Ball street
Goose, Mrs. Mary, Trowse Newton
Goose, William Henry, artist, No. 15, Briggs’ street
Goose, Mr. Robert, Union place
Goose, Robert, bricklayer and builder, Julian street
Goreham, John, copper and iron-plate worker, William street
Goreham, Henry, County Court bailiff, St. Lawrence lane
Goreham, Sarah, dressmaker, Lothian street
Goreham, William, shopkeeper, Rosemary lane
Gorell, Robert Atkinson, yarn agent, and cotton and silk merchant,
Muspole street; h Unthank’s road
Gosnold, Ellen Sarah, dressmaker, Surrey road
Gosnold, Henry George, solicitor’s clerk, Bethel street
Gostling, Francis, shoe manufacturer, (of the firm of Barker
Benjamin and Co.); h 9, Bedford street, Unthank’s road
Gostling, Richard, Robin Hood, Dereham load
Gotts, John, solicitor’s clerk, Norfolk street, Union place
Gotts, Miss Sarah, St. Stephen’s gates
Goulty, Charles, lodging-house keeper, 3, Vauxhall terrace, Julian
place
Gould, Rev. George, Baptist minister, Unthank’s road
Gowen, William, beer retailer, Lower Goat lane
Gower, James, carpenter, St. Julian street
Gower, Thomas, lemonade manufacturer, Gun lane
Gowing, Charles, harness maker, Castle hill
Gowing, George, farmer, Trowse Newton
Gowing, Rev. John, Baptist minister, Parry’s buildings, Philadelphia
Gowing, Samuel, butcher and green grocer, St. Benedict’s gates
Grand, Edward, tailor, 13, Upper King street
Grand, George, tailor and hatter, 2, Castle meadow
Grand, Mr. John, St. Giles’ street
Grand, Mr. John, Hall road, New Lakenham
Grand, John Fuller, solicitor’s clerk, Oxford street, Unthank’s road
Grand, John, fish salesman and auctioneer, Lady’s lane
Grand, Richard, Graham’s court, Upper market
Grand, Robert, boot and shoe maker, Duke street
Grand, Robert, merchant’s clerk, Catton road
Grant, Mr. Henry, Heigham road
Grant, Mrs. Sarah, Oxford street, Unthank’s road
Graver, Abraham, fruiterer, Magdalen street
Graver, John, butcher, Lower King street
Graver, Richard, shoemaker, Ber street
Graver, Thomas, baker, St. Paul’s plain
Graves, Mrs., Mount Pleasant
Gravener, Benjamin, shopkeeper, Lower Westwick street
Graves, John, market gardener, Dereham road
Gray, James, hair dresser, Bethel street
Gray, John, hair dresser, Rose lane
Gray, Mr. Joseph, Heigham grove, St. Giles’ road
Gray, Mrs. Rebecca, New road, Town close
Gray, Richard, tailor, Grapes’ hill
Gray, Mary Ann, pork butcher, Upper Westwick street, St. Swithin’s
Gray, Mary Ann, tailoress, Pottergate street
Green, Miss Ann, dressmaker, milliner, and straw bonnet maker,
and register office for servants, Post Office street
Green, Edward, clothier, Lower Westwick street
Green, Edward, whitesmith and bell-hanger, Duke street; h
Gildengate street
Green, Elizabeth, day school, Palace street
Green, George, cattle inspector, Brazen Doors road
Green, Hannah, dressmaker, St. Catherine’s terrace
Green, Isaac, commercial traveller, Sussex street, St. Clement’s
Green, James, green grocer, Philadelphia

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