Early results of the integrative epigenomic-transcriptomic landscape of colorectal adenoma and cancer

BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.

Identification of a novel mtDNA lineage B3 in chicken (Gallus gallus domesticus)

DEAR EDITOR, In this study, we sequenced the complete mitochondrial DNA genome （mitogenome） of the Zhengyang Yellow chicken （Gallus gallus domesticus） by next-generation sequencing technology. Samples were taken from Zhumadian city, Henan Province, China. The complete mitogenome was 16 785 bp in size, and had a nucleotide composition of 30.3% （A）, 23.7% （T） 32.5% （C）, and 13.5% （G）, with a high AT content of 54.0%. The assembled mitogenome exhibited typical mitochondrial DNA （mtDNA） structure, including a non-coding control region, two rRNA genes, 13 protein-coding genes, and 22 tRNA genes. Phylogenetic analysis indicated that this mitogenome defined a novel sub-haplogroup B3 within haplogroup B. These results should provide essential information for chicken domestication and insiqht into the evolution of genomes.

Direct evidence of CRISPR-Cas9-mediated mitochondrial genome editing

Pathogenic mitochondrial DNA(mtDNA)mutations can cause a variety of human diseases.The recent development of genome-editing technologies to manipulate mtDNA,such as mitochondria-targeted DNA nucleases and base editors,offer a promising way for curing mitochondrial diseases caused by mtDNA mutations.The CRISPR-Cas9 system is a widely used tool for genome editing;however,its application in mtDNA editing is still under debate.In this study,we developed a mito-Cas9 system by adding the mitochondria-targeted sequences and 30 untranslated region of nuclear-encoded mitochondrial genes upstream and downstream of the Cas9 gene,respectively.

Longitudinal transcriptome analyses show robust T cell immunity during recovery from COVID-19

Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell(PBMC)samples from 18 patients with coronavirus disease 2019(COVID-19)during their treatment,convalescence,and rehabilitation.After analyzing the regulatory networks of differentially expressed messenger RNAs(mRNAs),microRNAs(miRNAs)and long non-coding RNAs(lncRNAs)between the different clinical stages,we found that humoral immunity and type I interferon response were significantly downregulated,while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19.The formation of this T cell immune response might be driven by the activation of activating protein-1(AP-1)related signaling pathway and was weakly affected by other clinical features.These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.

Longitudinal transcriptome analyses show robust T cellimmunity during recovery from COVID-19

Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell(PBMC)samples from 18 patients with coronavirus disease 2019(COVID-19)during their treatment,convalescence,and rehabilitation.After analyzing the regulatory networks of differentially expressed messenger RNAs(mRNAs),microRNAs(miRNAs)and long non-coding RNAs(lncRNAs)between the different clinical stages,we found that humoral immunity and type I interferon response were significantly downregulated,while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19.The formation of this T cell immune response might be driven by the activation of activating protein-1(AP-1)related signaling pathway and was weakly affected by other clinical features.These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.