Advances of single-cell genomics and epigenomics in human disease: where are we now?

Abstract

Cellular heterogeneity is revolutionizing the way to study, monitor and dissect complex diseases. This has been possible with the technological and computational advances associated to single-cell genomics and epigenomics. Deeper understanding of cell-to-cell variation and its impact on tissue function will open new avenues for early disease detection, accurate diagnosis and personalized treatments, all together leading to the next generation of health care. This review focuses on the recent discoveries that single-cell genomics and epigenomics have facilitated in the context of human health. It highlights the potential of single-cell omics to further advance the development of personalized treatments and precision medicine in cancer, diabetes and chronic age-related diseases. The promise of single-cell technologies to generate new insights about the differences in function between individual cells is just emerging, and it is paving the way for identifying biomarkers and novel therapeutic targets to tackle age, complex diseases and understand the effect of life style interventions and environmental factors.

Profiling chromatin regulatory landscape: insights into the development of ChIP-seq and ATAC-seq

“…Although many algorithms have been developed to integrate multi-omics data, it is difficult to assess the performance of these algorithms and whether they fully preserve the biological variance. A growing number of studies in recent years have demonstrated the potential of parallel analysis of multiple modalities in the same cells [88][89][90]. Singlenucleus chromatin accessibility and mRNA expression sequencing (SNARE-seq) based on micro-droplet platform enables simultaneous sequencing of transcriptome and chromatin accessibility in a single cell by dual-omics capturing, and can appropriately correlate the results of both modalities to obtain detailed information on the regulation of gene expression [91].…”

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

“…That opens the door to decipher how genomic regulatory networks work [102]. Interestingly, these findings are particularly relevant for personalized treatments of complex diseases, such as cancer, diabetes and asthma, as well as chronic age-related diseases, due to the interaction of multiple genetic and environmental factors [13,163,164]. Indeed, new sequencing technologies have allowed epigenetic profiling of different cancers [78,165].…”

Epigenomics in the single cell era, an important read out for genome function and cell identity

“…Use of single-cell technologies can be essential to fully characterize the disease and to identify rare cell populations of regenerative potential. In fact, integration of data from Assay for Transposase-Accessible Chromatin sequencing and RNA-seq from FACS-sorted cell populations reveals that α-cells can transdifferentiate into β-cells [20,21], and have a more flexible epigenome with areas of open chromatin corresponding to β-cell signature genes. Such αto β-cell transition can be seen as a promising approach for β-cell regeneration and therapeutic solutions for diabetes [22].…”