Contents


Preface

The completion of the human genome sequence has driven the transition to the era of functional genomics, whose main contents are transcriptomics and proteomics. The human genome contains about 20,300 genes. However, the human transcriptome contains at least 100,000 transcripts, which is much more than the number of human genes due to RNA splicing and other factors during the transcription of a gene to RNA. Thus, multiple transcripts are often derived from one same gene. Each transcript guides the ribosome to synthesize an amino acid sequence of a protein. The synthesized protein in the ribosome must be translocated and redistributed to the appropriate locations to form a special conformation and interact with surrounding molecules, namely a complex, to exert its biological functions. Also, protein is modified by many posttranslational modifications (PTMs) and even unknown factors in the process of translocation and redistribution. There are about 400–600 PTMs in the human body, which are the main factors for the complexity and diversity of proteins, namely, protein species or proteoforms. Thus, multiple proteoforms are often derived from one same transcript. About 1,000,000 proteoforms are estimated to exist in the human body. Actually, a protein is a set of proteoforms. The different proteoforms derived from one gene might have different conformations and functions. A proteoform is the final functional performer of a gene. Proteoforms are the basic units in a proteome. Each proteoform has its own copy number or abundance. Therefore, proteoforms further enrich the concept and content of a proteome. Studies on proteoforms will offer much more in-depth insights into a proteome, which will directly lead to the discovery of reliable biomarkers for accurate understanding of molecular mechanisms, the discovery of effective therapeutic targets, and for effective prediction, diagnosis, and prognostic

This book focuses on the concept of proteoforms, technologies to study

concept of proteoforms, and compares the methods of "top-down" mass spectrometry and two-dimensional gel electrophoresis-liquid chromatographyliquid chromatography-mass spectrometry (2DE-LC/MS). Chapter 2 examines the general concepts of proteoforms and the methodological process for identifying them. Chapter 3 describes in detail how to prepare proteoforms of therapeutic proteins for top-down mass spectrometry analysis, which opens up an area for the application of proteoforms in medical science. Chapter 4 discusses prolactin proteoform pattern alteration in human pituitary adenomas

compared to control pituitary tissues, which provides an example of the application of proteoforms in clinical study. Chapter 5 covers proteoforms in acute leukemia, specifically evaluation of age- and disease-specific proteoform

of proteoforms. However, this book contains only a fraction of the very

This book presents new advances in the concept, methodology, and applications

proteoforms, and applications of proteoforms. Chapter 1 addresses the complete

assessment.

patterns.
