Integrated multi-omics profiling of nonfunctioning pituitary adenomas.

PURPOSE: Genetic and epigenetic alterations are involved in pituitary adenoma pathogenesis, however the molecular basis of proliferative nonfunctioning pituitary adenomas (NFPAs) remains unclear. Here, we analyzed integrated multi-omics profiling including copy number variation (CNV), DNA methylation and gene expression of 8 NFPAs. METHODS: We collected 4 highly proliferative (hpNFPA, Ki-67 ≥ 3) and 4 lowly proliferative (Ki-67 ≤ 1) NFPAs, and comprehensively assessed CNV, DNA methylation, and gene expression by Illumina HumanMethylation450 BeadChip and Affymetrix GeneChip PrimeView Human Gene Expression Array. We performed Ingenuity Pathway Analysis (IPA) for differentially expressed genes to illustrate aberrant pathways and delineated protein-protein networks of selected key genes in dysregulated pathways. RESULTS: Aberrant arm level CNV, dysregulated DNA methylation, and associated impacts on gene expressions were observed in 2 early occurring hpNFPAs. Chromosomal losses were associated with attenuated expression of DNA methyltransferases, further altering global methylation in these 2 samples. Correlation analysis between DNA methylation and gene expression in 8 NFPAs indicates methylation in promoter and gene body regions are both involved in gene regulation. IPA showed PPARα/RXRα, dopamine receptor signaling, cAMP-mediated signaling, and calcium signaling were all activated, while p38 MAPK and ERK5 signaling were inhibited in hpNFPAs. Moreover, selected key gene networks in hpNFPAs exhibited concurrent methylation status and expression levels of adenylate cyclase genes, G protein subunits, HLA genes, CXCL12, and CCL2. CONCLUSION: This study presents comprehensive multi-omics views of CNV, DNA methylation, and gene expression in 8 NFPAs. Pathway analysis and network maps of key genes provide clues to elucidate the molecular basis of hpNFPA.

First analysis of synonymous codon usage in porcine circovirus.

Porcine circovirus (PCV) is grouped into two types: PCV1 and PCV2. PCV1 is isolated from cultured cells and usually causes no clinical diseases in pigs. PCV2 is a pathogen of severe pig disease and a great threat to swine health and production. In our study, to investigate the codon usage bias of PCV, the genomic sequences of PCV1 and PCV2 were analyzed. The results showed that the codon usage bias of PCV was very low. An effective number of codons (ENC) plot analysis indicated that mutational pressure influences the codon usage bias of PCV. Neutrality plot analysis showed that mutation bias dominated over natural selection in shaping the codon usage bias of PCV1, but mutation bias and natural selection contributed equally to the codon usage bias of PCV2. Principal component analysis showed that different ORFs and dinucleotide patterns were also factors influencing the codon usage bias of PCV. Our study is helpful in understanding the codon usage pattern of PCV and the evolution of PCV.

Characterization of the porcine epidemic diarrhea virus codon usage bias.

Porcine epidemic diarrhea virus (PEDV) has been responsible for several recent outbreaks of porcine epidemic diarrhea (PED) and has caused great economic loss in the swine-raising industry. Considering the significance of PEDV, a systemic analysis was performed to study its codon usage patterns. The relative synonymous codon usage value of each codon revealed that codon usage bias exists and that PEDV tends to use codons that end in T. The mean ENC value of 47.91 indicates that the codon usage bias is low. However, we still wanted to identify the cause of this codon usage bias. A correlation analysis between the codon compositions (A3s, T3s, G3s, C3s, and GC3s), the ENC values, and the nucleotide contents (A%, T%, G%, C%, and GC%) indicated that mutational bias plays role in shaping the PEDV codon usage bias. This was further confirmed by a principal component analysis between the codon compositions and the axis values. Using the Gravy, Aroma, and CAI values, a role of natural selection in the PEDV codon usage pattern was also identified. Neutral analysis indicated that natural selection pressure plays a more important role than mutational bias in codon usage bias. Natural selection also plays an increasingly significant role during PEDV evolution. Additionally, gene function and geographic distribution also influence the codon usage bias to a degree.