This detailed book provides state-of-art computational approaches to further explore the exciting opportunities presented by single-cell technologies. Chapters each detail a computational toolbox aimed to overcome a specific challenge in single-cell analysis, such as data normalization, rare cell-type identification, and spatial transcriptomics analysis, all with a focus on hands-on implementation of computational methods for analyzing experimental data. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Computational Methods for Single-Cell Data Analysis aims to cover a wide range of tasks and serves as a vital handbook for single-cell data analysis.
It is difficult to imagine that the statistical analysis of compositional data has been a major issue of concern for more than 100 years. It is even more difficult to realize that so many statisticians and users of statistics are unaware of the particular problems affecting compositional data, as well as their solutions. The issue of ``spurious correlation'', as the situation was phrased by Karl Pearson back in 1897, affects all data that measures parts of some whole, such as percentages, proportions, ppm and ppb. Such measurements are present in all fields of science, ranging from geology, biology, environmental sciences, forensic sciences, medicine and hydrology. This book presents the history and development of compositional data analysis along with Aitchison's log-ratio approach. Compositional Data Analysis describes the state of the art both in theoretical fields as well as applications in the different fields of science. Key Features: Reflects the state-of-the-art in compositional data analysis. Gives an overview of the historical development of compositional data analysis, as well as basic concepts and procedures. Looks at advances in algebra and calculus on the simplex. Presents applications in different fields of science, including, genomics, ecology, biology, geochemistry, planetology, chemistry and economics. Explores connections to correspondence analysis and the Dirichlet distribution. Presents a summary of three available software packages for compositional data analysis. Supported by an accompanying website featuring R code. Applied scientists working on compositional data analysis in any field of science, both in academia and professionals will benefit from this book, along with graduate students in any field of science working with compositional data.
This book provides a clear and thorough introduction to meta-analysis, the process of synthesizing data from a series of separate studies. Meta-analysis has become a critically important tool in fields as diverse as medicine, pharmacology, epidemiology, education, psychology, business, and ecology. Introduction to Meta-Analysis: Outlines the role of meta-analysis in the research process Shows how to compute effects sizes and treatment effects Explains the fixed-effect and random-effects models for synthesizing data Demonstrates how to assess and interpret variation in effect size across studies Clarifies concepts using text and figures, followed by formulas and examples Explains how to avoid common mistakes in meta-analysis Discusses controversies in meta-analysis Features a web site with additional material and exercises A superb combination of lucid prose and informative graphics, written by four of the world’s leading experts on all aspects of meta-analysis. Borenstein, Hedges, Higgins, and Rothstein provide a refreshing departure from cookbook approaches with their clear explanations of the what and why of meta-analysis. The book is ideal as a course textbook or for self-study. My students, who used pre-publication versions of some of the chapters, raved about the clarity of the explanations and examples. David Rindskopf, Distinguished Professor of Educational Psychology, City University of New York, Graduate School and University Center, & Editor of the Journal of Educational and Behavioral Statistics. The approach taken by Introduction to Meta-analysis is intended to be primarily conceptual, and it is amazingly successful at achieving that goal. The reader can comfortably skip the formulas and still understand their application and underlying motivation. For the more statistically sophisticated reader, the relevant formulas and worked examples provide a superb practical guide to performing a meta-analysis. The book provides an eclectic mix of examples from education, social science, biomedical studies, and even ecology. For anyone considering leading a course in meta-analysis, or pursuing self-directed study, Introduction to Meta-analysis would be a clear first choice. Jesse A. Berlin, ScD Introduction to Meta-Analysis is an excellent resource for novices and experts alike. The book provides a clear and comprehensive presentation of all basic and most advanced approaches to meta-analysis. This book will be referenced for decades. Michael A. McDaniel, Professor of Human Resources and Organizational Behavior, Virginia Commonwealth University
This volume introduces Translational Bioinformatics as it relates to therapeutic development, and addresses the techniques needed to effectively translate large data sets to relevant biological networks. Chapters detail clinical informatics infrastructure, and leverage pathology, immunology, pharmacology, genomic, proteomic, and metabolomic informatics approaches. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, application details for both the expert and non-expert reader, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Translational Bioinformatics for Therapeutic Development: Methods and Protocols aims to ensure success in the study of Translational Bioinformatics.
Single-cell omics is a progressing frontier that stems from the sequencing of the human genome and the development of omics technologies, particularly genomics, transcriptomics, epigenomics and proteomics, but the sensitivity is now improved to single-cell level. The new generation of methodologies, especially the next generation sequencing (NGS) technology, plays a leading role in genomics related fields; however, the conventional techniques of omics require number of cells to be large, usually on the order of millions of cells, which is hardly accessible in some cases. More importantly, harnessing the power of omics technologies and applying those at the single-cell level are crucial since every cell is specific and unique, and almost every cell population in every systems, derived in either vivo or in vitro, is heterogeneous. Deciphering the heterogeneity of the cell population hence becomes critical for recognizing the mechanism and significance of the system. However, without an extensive examination of individual cells, a massive analysis of cell population would only give an average output of the cells, but neglect the differences among cells. Single-cell omics seeks to study a number of individual cells in parallel for their different dimensions of molecular profile on genome-wide scale, providing unprecedented resolution for the interpretation of both the structure and function of an organ, tissue or other system, as well as the interaction (and communication) and dynamics of single cells or subpopulations of cells and their lineages. Importantly single-cell omics enables the identification of a minor subpopulation of cells that may play a critical role in biological process over a dominant subpolulation such as a cancer and a developing organ. It provides an ultra-sensitive tool for us to clarify specific molecular mechanisms and pathways and reveal the nature of cell heterogeneity. Besides, it also empowers the clinical investigation of patients when facing a very low quantity of cell available for analysis, such as noninvasive cancer screening with circulating tumor cells (CTC), noninvasive prenatal diagnostics (NIPD) and preimplantation genetic test (PGT) for in vitro fertilization. Single-cell omics greatly promotes the understanding of life at a more fundamental level, bring vast applications in medicine. Accordingly, single-cell omics is also called as single-cell analysis or single-cell biology. Within only a couple of years, single-cell omics, especially transcriptomic sequencing (scRNA-seq), whole genome and exome sequencing (scWGS, scWES), has become robust and broadly accessible. Besides the existing technologies, recently, multiplexing barcode design and combinatorial indexing technology, in combination with microfluidic platform exampled by Drop-seq, or even being independent of microfluidic platform but using a regular PCR-plate, enable us a greater capacity of single cell analysis, switching from one single cell to thousands of single cells in a single test. The unique molecular identifiers (UMIs) allow the amplification bias among the original molecules to be corrected faithfully, resulting in a reliable quantitative measurement of omics in single cells. Of late, a variety of single-cell epigenomics analyses are becoming sophisticated, particularly single cell chromatin accessibility (scATAC-seq) and CpG methylation profiling (scBS-seq, scRRBS-seq). High resolution single molecular Fluorescence in situ hybridization (smFISH) and its revolutionary versions (ex. seqFISH, MERFISH, and so on), in addition to the spatial transcriptome sequencing, make the native relationship of the individual cells of a tissue to be in 3D or 4D format visually and quantitatively clarified. On the other hand, CRISPR/cas9 editing-based In vivo lineage tracing methods enable dynamic profile of a whole developmental process to be accurately displayed. Multi-omics analysis facilitates the study of multi-dimensional regulation and relationship of different elements of the central dogma in a single cell, as well as permitting a clear dissection of the complicated omics heterogeneity of a system. Last but not the least, the technology, biological noise, sequence dropout, and batch effect bring a huge challenge to the bioinformatics of single cell omics. While significant progress in the data analysis has been made since then, revolutionary theory and algorithm logics for single cell omics are expected. Indeed, single-cell analysis exert considerable impacts on the fields of biological studies, particularly cancers, neuron and neural system, stem cells, embryo development and immune system; other than that, it also tremendously motivates pharmaceutic RD, clinical diagnosis and monitoring, as well as precision medicine. This book hereby summarizes the recent developments and general considerations of single-cell analysis, with a detailed presentation on selected technologies and applications. Starting with the experimental design on single-cell omics, the book then emphasizes the consideration on heterogeneity of cancer and other systems. It also gives an introduction of the basic methods and key facts for bioinformatics analysis. Secondary, this book provides a summary of two types of popular technologies, the fundamental tools on single-cell isolation, and the developments of single cell multi-omics, followed by descriptions of FISH technologies, though other popular technologies are not covered here due to the fact that they are intensively described here and there recently. Finally, the book illustrates an elastomer-based integrated fluidic circuit that allows a connection between single cell functional studies combining stimulation, response, imaging and measurement, and corresponding single cell sequencing. This is a model system for single cell functional genomics. In addition, it reports a pipeline for single-cell proteomics with an analysis of the early development of Xenopus embryo, a single-cell qRT-PCR application that defined the subpopulations related to cell cycling, and a new method for synergistic assembly of single cell genome with sequencing of amplification product by phi29 DNA polymerase. Due to the tremendous progresses of single-cell omics in recent years, the topics covered here are incomplete, but each individual topic is excellently addressed, significantly interesting and beneficial to scientists working in or affiliated with this field.
The State of the Art in Transcriptome AnalysisRNA sequencing (RNA-seq) data offers unprecedented information about the transcriptome, but harnessing this information with bioinformatics tools is typically a bottleneck. RNA-seq Data Analysis: A Practical Approach enables researchers to examine differential expression at gene, exon, and transcript le
The Mouse Nervous System provides a comprehensive account of the central nervous system of the mouse. The book is aimed at molecular biologists who need a book that introduces them to the anatomy of the mouse brain and spinal cord, but also takes them into the relevant details of development and organization of the area they have chosen to study. The Mouse Nervous System offers a wealth of new information for experienced anatomists who work on mice. The book serves as a valuable resource for researchers and graduate students in neuroscience. Systematic consideration of the anatomy and connections of all regions of the brain and spinal cord by the authors of the most cited rodent brain atlases A major section (12 chapters) on functional systems related to motor control, sensation, and behavioral and emotional states A detailed analysis of gene expression during development of the forebrain by Luis Puelles, the leading researcher in this area Full coverage of the role of gene expression during development and the new field of genetic neuroanatomy using site-specific recombinases Examples of the use of mouse models in the study of neurological illness
This book provides an up-to-date review of classic and advanced bioinformatics approaches and their utility in rice research. It summarizes databases and tools for analyzing DNA, proteins and gene expression profiles, mapping genetic variations, annotation of protein and RNA molecules, phylogenetic analysis, and pathway enrichment. In addition, it presents high-throughput technologies that are widely used to provide deep insights into the genetic architecture of important traits in the rice genome. The book subsequently discusses techniques for identifying RNA-protein, DNA-protein interactions, and molecular markers, including SNP and microsatellites, in the contexts of rice breeding and genetics. Lastly, it explores various tools that are used to identify and characterize non-coding RNA in rice and their potential role in rice research.
This volume provides a comprehensive overview for investigating biology at the level of individual cells. Chapters are organized into eight parts detailing a single-cell lab, single cell DNA-seq, RNA-seq, single cell proteomic and epigenetic, single cell multi-omics, single cell screening, and single cell live imaging. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Single Cell Methods: Sequencing and Proteomics aims to make each experiment easily reproducible in every lab.
