Biology subjects

Lei, R.

Publications and source records attributed to Lei, R..

21 records · Page 2Linked to original sources

bioRxiv2021

The methylation of SDC2 and TFPI2 defined three methylator phenotypes of colorectal cancer

Methylation-based noninvasive molecular diagnostics are easy and feasible tools for the early detection of colorectal cancer (CRC). However, many of them have the limitation of low sensitivity with some CRCs detection failed in clinical practice. In this study, the clinical and pathological characteristics, as well as molecular features of three methylator-groups, defined by the promoter methylation status of SDC2 and TFPI2, were investigated in order to improve the performance of CRC detection. The Illumina Infinium 450k Human DNA methylation data and clinical information of CRCs were collected from The Cancer Genome Atlas (TCGA) project and Gene Expression Omnibus (GEO) database. CRC samples were divided into three groups, HH (dual-positive), HL (single positive) and LL (dual-negative) according to the methylation status of SDC2 and TFPI2 promoters. Differences in age, tumor location, microsatellite instable status and differentially expressed genes (DEGs) were evaluated among the three groups and these findings were then confirmed in our inner CRC dataset. The combination of methylated SDC2 and TFPI2 showed a superior performance of distinguishing CRCs from normal controls than each alone. Samples of HL group were more often originated from left-side CRCs whereas very few of them were from right-side (P < 0.05). HH grouped CRCs showed a higher level of microsatellite instability and mutation load than other two groups (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). All mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were found in HH group (HH/HL/LL: 51/0/0, P = 0.018). Also there was a significantly older patient age at the diagnosis in HH group. Gene expression analysis identified 37, 84 and 22 group-specific DEGs for HH, HL and LL, respectively. Functional enrichment analysis suggested that HH specific DEGs were mainly related to the regulation of transcription and other processes, while LL specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration. The three defined mathylator groups showed great difference in tumor location, patient age, MSI and ECM biological process, which could facilitate the development of more effective biomarkers for CRC detection.

cancer biology↗

bioRxiv2020

bHLH11 negatively regulates Fe homeostasis by its EAR motifs recruiting corepressors in Arabidopsis

Iron (Fe) homeostasis is essential for plant growth and development. Many transcription factors play pivotal roles in the maintenance of Fe homeostasis. bHLH11 was identified as a negative transcription factor regulating Fe homeostasis, however, the underlying molecular mechanism remains elusive. We generated two loss-of-function bhlh11 mutants which display the enhanced sensitivity to Fe excess, the increased Fe accumulation and the elevated expression of Fe deficiency responsive genes. bHLH11 protein, localized in both the cytoplasm and nucleus, decreases in response to Fe deficiency. Coexpression assays indicate that bHLH IVc transcription factors (TFs) (bHLH34, bHLH104, bHLH105, and bHLH115) facilitate the nuclear accumulation of bHLH11 protein. Further analysis indicates that bHLH11 represses the transactivity of bHLH IVc TFs towards bHLH Ib genes (bHLH38, bHLH39, bHLH100, and bHLH101). bHLH11 contains two EAR motifs which are responsible for the repression function by recruiting the TOPLESS/TOPLESS-RELATED (TPL/TPRs) corepressors. Correspondingly, the expression of Fe uptake genes increases in the tpr1 tpr4 tpl mutant. Moreover, genetic analysis reveals that bHLH11 has functions independent of FIT. This study provides insights into the complicate Fe homeostasis signaling network. One-sentence summarybHLH IVc proteins promote the bHLH11 protein accumulation in the nucleus where bHLH11 inhibits the transcriptional activation ability of bHLH IVc via its EAR motifs recruiting the TOPLESS/TOPLESS-RELATED corepressors.

plant biology↗

bioRxiv2019

High accuracy DNA sequencing on a small, scalable platform via electrical detection of single base incorporations

High throughput DNA sequencing technologies have undergone tremendous development over the past decade. Although optical detection-based sequencing has constituted the majority of data output, it requires a large capital investment and aggregation of samples to achieve optimal cost per sample. We have developed a novel electronic detection-based platform capable of accurately detecting single base incorporations. The GenapSys technology with its electronic detection modality allows the system to be compact, accessible, and affordable. We demonstrate the performance of the system by sequencing several different microbial genomes with varying GC content. The platform is capable of generating up to 2 Gb of high-quality nucleic acid sequence in a single run. We routinely generate sequence data that exceeds 99% raw accuracy with read lengths of up to 175 bp. Average quality scores remain above Q30 (99.9% raw sequencing accuracy) beyond 150 bp, with more than 85% of total bases at or above Q30. The utility of the platform is highlighted by targeted sequencing of the human genome. We show high concordance of SNP detection on the human NA12878 HapMap cell line with data generated on the Illumina sequencing platform. In addition, we sequenced a targeted panel of cancer-associated genes in a well characterized reference standard. With multiple library preparation approaches on this sample, we were able to identify low frequency mutations at expected allele frequencies.

genomics↗