Potentials of single-cell biology in identification and validation of disease biomarkers

Abstract

Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers.

Keywords: gene sequencing; genome function; heterogeneity; mechanical phenotypes; single-cell biology.

Figure 1

The complexity of single‐cell biology consists of single‐molecule function, molecular networks and interaction, transcriptional signals, systems biology and genome function.

Figure 2

A workflow of clinical example to investigate single‐cell biology for the identification and validation of disease‐specific biomarkers. For example, bronchial single epithelial cells are isolated and purified by brushing the bronchial surface (A) or/and taking biopsies from pathological foci (B) of patients, e.g. with airway diseases after the collection of clinical information on patient phenotypes, biochemical measurements, molecular imaging, therapies and responses (C). Those single cells are applied for the measurement of gene expression, sequencing, epigenetics and function, and proteomic profiling, by integrating with the validation of intact single‐cell culture and function. Selected candidate biomarkers are furthermore validated and investigated in clinical systems, e.g. patient information, imaging, pathology and organ function.

Figure 3

Presence of heterogeneity or variability among species, populations, patients, inter‐organs/tissues, intra‐tumour locations, cells within a location, gene mutations and variations, and 3D architecture and organization of genome function.