Springer Handbooks of Computational Statistics

Handbook of Statistical Bioinformatics (2nd Edition) Lu

Henry Horng-Shing Lu
Bernhard Schölkopf
www.yakibooki.com/download/handbook-of-statistical-bioinformatics-2nd
Martin T. Wells
Hongyu Zhao Editors

Handbook
of Statistical
Bioinformatics
Second Edition

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 Handbook of Statistical Bioinformatics (2nd Edition) Lu
Springer Handbooks of Computational Statistics

Series Editors
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James E. Gentle, George Mason University, Fairfax, VA, USA
Wolfgang Karl Härdle, Humboldt-Universität zu Berlin, Berlin, Germany
Yuichi Mori, Okayama University of Science, Okayama, Japan

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 Handbook of Statistical Bioinformatics (2nd Edition) Lu
Henry Horng-Shing Lu • Bernhard Schölkopf •
Martin T. Wells • Hongyu Zhao
Editors
www.yakibooki.com/download/handbook-of-statistical-bioinformatics-2nd

Handbook of Statistical
Bioinformatics

This Book is Available on YakiBooki.com

 Handbook of Statistical Bioinformatics (2nd Edition) Lu
Editors
Henry Horng-Shing Lu Bernhard Schölkopf
Institute of Statistics Department of Empirical Inference
National Yang Ming Chiao Tung University Max Planck Institute for Intelligent Systems
Hsinchu, Taiwan, ROC Tübingen, Germany

www.yakibooki.com/download/handbook-of-statistical-bioinformatics-2nd
Martin T. Wells Hongyu Zhao
Department of Statistics and Data Science Department of Biostatistics
Cornell University Yale University
Ithaca, NY, USA New Haven, CT, USA

ISSN 2197-9790 ISSN 2197-9804 (electronic)

Springer Handbooks of Computational Statistics
ISBN 978-3-662-65901-4 ISBN 978-3-662-65902-1 (eBook)
https://doi.org/10.1007/978-3-662-65902-1

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer-Verlag GmbH,
DE, part of Springer Nature 2011, 2022
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
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Springer Nature.
The registered company address is: Heidelberger Platz 3, 14197 Berlin, Germany

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 Handbook of Statistical Bioinformatics (2nd Edition) Lu
Preface

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Numerous fascinating and important breakthroughs in biotechnology have gen-

erated massive volumes of high throughput data with diverse types that demand
novel developments of efficient and appropriate tools in computational statistics
that are integrated with biological knowledge and computational algorithms. This
updated volume collects contributed chapters from leading researchers to survey
many recent active research topics that have developed since the previous edition of
the Handbook of Statistical Bioinformatics. This updated handbook is intended to
serve as both an introductory and reference monograph for students and researchers
who are interested in learning the state-of-the-art developments in computational
statistics as applied to computational biology.
This collection of articles, from the leading scholars in the field, is primarily a
monograph which will be of interest to the educational, academic, and professional
organizations related to statisticians, computer scientists, biological and biomedical
researchers with strong interests in computational biology. Although there are other
volumes available for computational statistics and bioinformatics on the market,
there are few books such as this that focus on the interface between computational
statistics and cutting-edge developments in computational biology. Seeing this need,
this completely updated collection is aimed to establish this bridge. This handbook
covers many significant up-to-date topics in probabilistic and statistical modeling
as well as the analysis of massive data sets generated from modern biotechnology.
These methods and technologies will change the perspectives of biology, healthcare,
and medicine in the twenty-first century! This collection is an extended version
of the previous edited handbook. The advanced research topics cover statistical
methods for single-cell analysis, network analysis, and systems biology.
During the editing process of this handbook, the world has been upended by
the massive influence of COVID-19 pandemic and other challenges. The editors
would like to thank the contributing authors, Springer management team members,

v
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 vi Preface
Handbook of Statistical Bioinformatics (2nd Edition) Lu
supporting colleagues and family members for their incredible support and patience
during this challenging time period in order for this handbook to be made available
to the related scholarly communities!

Hsinchu, Taiwan, ROC Henry Horng-Shing Lu

www.yakibooki.com/download/handbook-of-statistical-bioinformatics-2nd
Tübingen, Germany Bernhard Schölkopf
Ithaca, NY, USA Martin T. Wells
New Haven, CT, USA Hongyu Zhao
May 8, 2022

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 Handbook of Statistical Bioinformatics (2nd Edition) Lu
Contents

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Part I Single-Cell Analysis

Computational and Statistical Methods for Single-Cell RNA
Sequencing Data.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3
Zuoheng Wang and Xiting Yan
Pre-processing, Dimension Reduction, and Clustering for
Single-Cell RNA-seq Data .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 37
Jialu Hu, Yiran Wang, Xiang Zhou, and Mengjie Chen
Integrative Analyses of Single-Cell Multi-Omics Data: A Review
from a Statistical Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 53
Zhixiang Lin
Approaches to Marker Gene Identification from Single-Cell
RNA-Sequencing Data .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 71
Ronnie Y. Li, Wenjing Ma, and Zhaohui S. Qin
Model-Based Clustering of Single-Cell Omics Data.. . . . .. . . . . . . . . . . . . . . . . . . . 85
Xinjun Wang, Haoran Hu, and Wei Chen
Deep Learning Methods for Single-Cell Omics Data.. . . .. . . . . . . . . . . . . . . . . . . . 109
Jingshu Wang and Tianyu Chen

Part II Network Analysis

Probabilistic Graphical Models for Gene Regulatory Networks . . . . . . . . . . . 135
Zhenwei Zhou, Xiaoyu Zhang, Peitao Wu, and Ching-Ti Liu
Additive Conditional Independence for Large and Complex
Biological Structures .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 153
Kuang-Yao Lee, Bing Li, and Hongyu Zhao
Integration of Boolean and Bayesian Networks . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 173
Meng-Yuan Tsai and Henry Horng-Shing Lu

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 viii Contents
Handbook of Statistical Bioinformatics (2nd Edition) Lu
Computational Methods for Identifying MicroRNA-Gene
Regulatory Modules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 187
Yin Liu
Causal Inference in Biostatistics .. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 209
Shasha Han and Xiao-Hua Zhou
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Bayesian Balance Mediation Analysis in Microbiome Studies . . . . . . . . . . . . . . 237
Lu Huang and Hongzhe Li

Part III Systems Biology

Identifying Genetic Loci Associated with Complex Trait Variability . . . . . . 257
Jiacheng Miao and Qiongshi Lu
Cell Type-Specific Analysis for High-throughput Data ... . . . . . . . . . . . . . . . . . . . 271
Ziyi Li and Hao Wu
Recent Development of Computational Methods in the Field
of Epitranscriptomics .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 285
Zijie Zhang, Shun Liu, Chuan He, and Mengjie Chen
Estimation of Tumor Immune Signatures from Transcriptomics Data . . . . 311
Xiaoqing Yu
Cross-Linking Mass Spectrometry Data Analysis . . . . . . . .. . . . . . . . . . . . . . . . . . . . 339
Chen Zhou and Weichuan Yu
Cis-regulatory Element Frequency Modules and their Phase
Transition across Hominidae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 371
Lei M Li, Mengtian Li, and Liang Li
Improved Method for Rooting and Tip-Dating a Viral Phylogeny . . . . . . . . . 397
Xuhua Xia

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 Handbook of Statistical Bioinformatics (2nd Edition) Lu
Part I
Single-Cell Analysis

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 Handbook of Statistical Bioinformatics (2nd Edition) Lu
Computational and Statistical Methods
for Single-Cell RNA Sequencing Data

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Zuoheng Wang and Xiting Yan

Abstract In recent years, advances in droplet-based technology have boosted

the popularity of using single-cell RNA sequencing (scRNA-seq) technology to
investigate transcriptomic and cell population composition changes in various
tissues and diseases. Despite the potential of these technologies in understanding
disease pathogenesis and developing novel personalized therapeutics, analyses
of the generated scRNA-seq data are challenging, mainly due to high noise
level, prevalent dropout events, heterogeneous sources of variation confounding
phenotype of interest, and so on. In this chapter, we introduce these challenges in
analyses of scRNA-seq data and the corresponding computational and statistical
methods developed to address them. The topics include data preprocessing, data
normalization, dropout imputation, and differential expression analysis.

1 Introduction

Gene expression profiling measures levels of mRNA to understand transcriptomic

changes due to disease, treatment, environment, time, and so on. Traditional bulk
RNA gene expression profiling using microarrays and RNA sequencing pools RNAs
from a large population of cells consisting of various and often unknown cell types.
It measures the average expression profile in mixed cell populations with unknown
contribution from different cells or cell types. Thus, bulk RNA gene expression
data is unable to precisely identify the cellular source of transcriptomic changes of
interest, especially when high cell-to-cell heterogeneity exists [1–5]. To investigate
transcriptomic changes at single-cell resolution, two major challenges exist includ-
ing (1) isolating cells from each other without strong perturbations to cells that
lead to systematic transcriptomic changes and (2) amplification of extremely low

Z. Wang · X. Yan ()

Yale University, New Haven, CT, USA
e-mail: [email protected]; [email protected]

© The Author(s), under exclusive license to Springer-Verlag GmbH, DE, 3

part of Springer Nature 2022
H. H.-S. Lu et al. (eds.), Handbook of Statistical Bioinformatics,
Springer Handbooks of Computational Statistics,
https://doi.org/10.1007/978-3-662-65902-1_1
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