• GWAS (Genome-wide association study) is an approach to associate genetic variants with traits (such as human height, or even diseases). However, every cell in your body has the same DNA. It is a challenge of using GWAS to identify which type of tissue or cell types associated with certain diseases. In recent Nature communications, Researchers in Broad and MIT performed massively parallel single-cell RNA sequencing in two platforms: droplet-based microfluidics and nanowell-based Seq-well.
  • The nervous system exhibits the most extensive usage of pre-mRNA alternative transcript isoforms. However, it remains debated as to what extent pre-mRNA alternative splicing events detected by RNA-seq are indeed recruited for translation to produce proteins. Ribosome-seq uses specialized messenger RNA sequencing to determine which mRNAs are being actively translated (Fig. 1), it only targets mRNA protected by the ribosome during the process of decoding by translation.
  • Characterization of host cell response of viral infection is of great interest. Deep insights into molecular signatures of specific cell subsets to viral infection will provide potential antiviral therapies. In recent Nature communications, Researchers in Germany used Herpesvirus (HSV) infection as a virus-host model, performed single-cell RNA-sequencing of HSV-1 infected primary fibroblasts at different infection time points.
  • Population stratification is the presence of a systematic difference in allele frequencies between subpopulations in a population, which possibly due to different ancestry, especially in the context of association studies ( Precision Medicine must rely on these structured data, analyze the health of patient populations, then make clinical decisions.
  • The Cancer Genome Atlas (TCGA) Program has sequenced over 20, 000 cancers of 33 cancer types (, and revealed many mutational signatures underlying the biological process. However, cancers are end stages of an evolutionary process, which commonly arise through the accumulation of several driver mutations that engender a series of cancer cell clonal expansions.
  • Unlike next-generation sequencing (specifically, Illumina Sequencing by Synthesis Technology), new third-generation sequencing is being developed to overcome limitations such as amplification biases, short reads (reads size < 300 bp). Oxford Nanopore Technology uses nanopore-based sequencing to detect changes in current as a single strand of nucleic acid sequence transverses a pore protein.
  • Tumor heterogeneity is the critical factor harboring resistance mechanisms. During drug treatment, the evolutionary pressure drives outgrowth of distinct tumor subclones, which finally results in acquired resistance of current targeted therapies.
  • Modification to RNA species has been discovered for over 50 years. The internal modification m6A N6-methyladenosine (m6A) is the most abundant type, plays diverse roles in a variety of physiological processes. To date, most global m6A detection relies on RNA immunoprecipitation by m6A-recognizing antibodies, such as MeRIP-seq, m6A-seq. These methods are time-consuming and costly (expensive antibody, a large amount of input RNA).
  • DNA methylation and demethylation are tightly regulated, they shape chromatin accessibility and control gene expression during development. The Ten-Eleven Translocation (TET) genes play important role in DNA methylation and demethylation homeostasis. In recent Nature communications, researchers in Texas A&M University used Tet2, Tet3 mice deletion mouse model, analyzed DNA methylation dynamics and organization during early heart development.
  • Glioblastoma multiforme (GBM) is the deadliest and most common type of malignant primary brain tumor in adults. Symptoms of GBM include seizure, nausea, headache, as well as progressive neurological and psychological deficit. Patients with GBM have a dismal prognosis: the median survival time after diagnosis is approximately 15 months, and the 5-year survival rate is only 4%.