Bioinformatics Approaches to Single-Cell Analysis in Developmental Biology

Authors

Dicle Yalcin, University of Nebraska-LincolnFollow
Zeynep M. HakguderFollow
Hasan H. Otu, University of Nebraska-LincolnFollow

Date of this Version

9-2015

Citation

Published in Molecular Human Reproduction (2015) doi: 10.1093/molehr/gav050 Advance published online: September 10, 2015

Comments

Copyright © 2015 Dicle Yalcin, Zeynep M. Hakguder, and Hasan H. Otu. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. Used by permission.

Abstract

Individual cells within the same population show various degrees of heterogeneity, which may be better handled with single-cell analysis to address biological and clinical questions. Single-cell analysis is especially important in developmental biology as subtle spatial and temporal differences in cells have significant associations with cell fate decisions during differentiation and with the description of a particular state of a cell exhibiting an aberrant phenotype. Biotechnological advances, especially in the area of microfluidics, have led to a robust, massively parallel and multi-dimensional capturing, sorting, and lysis of single-cells and amplification of related macromolecules, which have enabled the use of imaging and omics techniques on single-cells. There have been improvements in computational single-cell image analysis in developmental biology regarding feature extraction, segmentation, image enhancement, and machine learning, handling limitations of optical resolution to gain new perspectives from the raw microscopy images. Omics approaches, such as transcriptomics, genomics, and epigenomics, targeting gene and small RNA expression, single nucleotide and structural variations, and methylation and histone modifications, rely heavily on high-throughput sequencing technologies. Although there are well-established bioinformatics methods for analysis of sequence data, there are limited bioinformatics approaches which address experimental design, sample size considerations, amplification bias, normalization, differential expression, coverage, clustering, and classification issues, specifically applied at the single-cell level. In this review, we summarize biological and technological advancements, discuss challenges faced in the aforementioned data acquisition and analysis issues, and present future prospects for application of single-cell analyses to developmental biology.