A review of disease risk prediction methods and applications in the omics era.

Risk prediction and disease prevention are the innovative care challenges of the 21st century. Apart from freeing the individual from the pain of disease, it will lead to low medical costs for society. Until very recently, risk assessments have ushered in a new era with the emergence of omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and so on, which potentially advance the ability of biomarkers to aid prediction models. While risk prediction has achieved great success, there are still some challenges and limitations. We reviewed the general process of omics-based disease risk model construction and the applications in four typical diseases. Meanwhile, we highlighted the problems in current studies and explored the potential opportunities and challenges for future clinical practice.

Effects of genetic variation on the structure of RNA and protein.

Changes in the structure of RNA and protein, have an important impact on biological functions and are even important determinants of disease pathogenesis and treatment. Some genetic variations, including copy number variation, single nucleotide variation, and so on, can lead to changes in biological function and increased susceptibility to certain diseases by changing the structure of RNA or protein. With the development of structural biology and sequencing technology, a large amount of RNA and protein structure data and genetic variation data resources has emerged to be used to explain biological processes. Here, we reviewed the effects of genetic variation on the structure of RNAs and proteins, and investigated their impact on several diseases. An online resource (http://www.onethird-lab.com/gems/) to support convenient retrieval of common tools is also built. Finally, the challenges and future development of the effects of genetic variation on RNA and protein were discussed.

Measurement of the apical anatomy of immature maxillary central incisors using cone-beam computed tomography.

OBJECTIVE: To investigate the CBCT findings of the apical anatomy of immature maxillary central incisors. METHODS: CBCT images of 100 immature maxillary central incisors in Nolla 8 and 100 immature maxillary central incisors in Nolla 9 were collected. The mesiodistal and carniocaudal diameters of the apical foramen of immature maxillary central incisors were measured by software included with CBCT, as well as the mesiodistal, carniocaudal and facioligual diameters of the apical shadow. The apical shadow and apical foramen diameters were compared between Nolla 8 and Nolla 9. Data were analyzed using the MedCalc software package. RESULTS: For immature maxillary central incisors, the mesiodistal and facioligual diameters of the apical foramen were 2.75±0.68 mm and 3.28±0.74 mm in Nolla 8 and 1.50±0.51 mm and 1.92±0.79 mm in Nolla 9. The mesiodistal, facioligual and carniocaudal diameters of the apical shadow were 3.84±0.73 mm, 4.49±0.68 mm and 3.41±1.27 mm in Nolla 8 and 2.76±0.60 mm, 3.41±0.80 mm and 2.06±0.65 mm in Nolla 9, respectively. CONCLUSIONS: The immature maxillary central incisors in Nolla 8 have a larger apical shadow and apical foramen than those in Nolla 9. The apical region of the maxillary central incisors in Nolla 8 was more likely to have a broad, blurred lamina dura. With the development of the apical foramen, the lamina dura in the apical region tended to be clear and sharp. CLINICAL SIGNIFICANCE: To our knowledge, this is the first study to radiologically analyse the in vivo anatomy of the apical foramen and apical shadow of immature maxillary central incisors. The results of this study provide a more detailed understanding of the apical anatomy of the immature maxillary central incisor for the diagnosis and treatment of apical lesions.

Genome-wide identification of m6A-associated single nucleotide polymorphisms in complex diseases of nervous system.

N6-methyladenosine (m6A) is one of the most abundant chemical modifications on RNA and can affect the occurrence and development of diseases. Some studies have shown that the expressions of some m6A-related genes are significantly regulated by single nucleotide variants (SNV). However, the function of m6A-associated single nucleotide polymorphisms (m6A-SNP) remains unclear in multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Here, we identified the disease-associated m6A-SNPs by integrating genome-wide association study (GWAS) and m6A-SNPs from the RMVar database, and confirmed the relationship between these identified m6A-SNPs and their target genes in eQTL analysis and gene differential expression analysis. Finally, 26 genes corresponding to 20 m6A-SNPs with eQTL signals were identified and differentially expressed (P < 0.05) in MS, 15 genes corresponding to 12 m6A-SNPs (P < 1e-04) were differentially expressed in AD, and 27 PD-associated m6A-SNPs that regulated the expression of 31 genes were identified. There were 5 HLA genes with eQTL signals (HLA-DQB1, HLA-DRB1, HLA-DQA1, HLA-DQA2 and HLA-DQB1-AS1) to be detected in the three diseases. In summary, our study provided new insights into understanding the potential roles of these m6A-SNPs in disease pathogenesis as well as therapeutic target.

RABC: Rheumatoid Arthritis Bioinformatics Center.

Advances in sequencing technologies have led to the rapid growth of multi-omics data on rheumatoid arthritis (RA). However, a comprehensive database that systematically collects and classifies the scattered data is still lacking. Here, we developed the Rheumatoid Arthritis Bioinformatics Center (RABC, http://www.onethird-lab.com/RABC/), the first multi-omics data resource platform (data hub) for RA. There are four categories of data in RABC: (i) 175 multi-omics sample sets covering transcriptome, epigenome, genome, and proteome; (ii) 175 209 differentially expressed genes (DEGs), 105 differentially expressed microRNAs (DEMs), 18 464 differentially DNA methylated (DNAm) genes, 1 764 KEGG pathways, 30 488 GO terms, 74 334 SNPs, 242 779 eQTLs, 105 m6A-SNPs and 18 491 669 meta-mQTLs; (iii) prior knowledge on seven types of RA molecular markers from nine public and credible databases; (iv) 127 073 literature information from PubMed (from 1972 to March 2022). RABC provides a user-friendly interface for browsing, searching and downloading these data. In addition, a visualization module also supports users to generate graphs of analysis results by inputting personalized parameters. We believe that RABC will become a valuable resource and make a significant contribution to the study of RA.

The analysis of root canal curvature and direction of maxillary lateral incisors by using cone-beam computed tomography: A retrospective study.

ABSTRACT: The aim of this study was to investigate root canal curvature and direction of maxillary lateral incisors in Shandong, China.Cone beam computed tomography (CBCT) images of 176 maxillary lateral incisors of 88 patients were collected in Shandong Province, China. Software included with CBCT was used to measure the angle of root canal curvature of maxillary lateral incisors on the maximum bending plane. In addition, the direction of each root canal was recorded. The data were statistically analyzed by SPSS 17.0 software package.The results showed that all the samples had a single canal (Vertucci's type I). The incidence of straight root canals, curved root canals, and S-type root canals was 39.2%, 58%, and 2.8%, respectively. The difference in the mean angle of root canal curvature failed to identify any differences between the left and right side (P > .05). The most curved root canal of maxillary lateral incisors oriented in the palato-distal direction.The maxillary lateral incisors were mainly curved root canals of which the proportion of moderate curvature was the largest. Software included with CBCT would provide some valuable information for root canal instrumentation of maxillary lateral incisors.

The relaxin gene knockout mouse: a model of progressive scleroderma.

Relaxin is a peptide hormone with anti-fibrotic properties. To investigate the long-term effects of relaxin deficiency on the ageing skin, we compared structural changes in the skin of ageing relaxin-deficient (RLX-/-) and normal (RLX+/+) mice, by biochemical, histological, and magnetic resonance imaging analyses. Skin biopsies from RLX+/+ and RLX-/- mice were obtained at different ages and analyzed for changes in collagen expression and distribution. We demonstrated an age-related progression of dermal fibrosis and thickening in male and female RLX-/- mice, associated with marked increases in types I and III collagen. The increased collagen was observed primarily in the dermis of RLX-/- mice by 1 mo of age, and eventually superseded the hypodermal layer. Additionally, fibroblasts from the dermis of RLX-/- mice were shown to produce increased collagen in vitro. Recombinant human gene-2 (H2) relaxin treatment of RLX-/- mice resulted in the complete reversal of dermal fibrosis, when applied to the early onset of disease, but was ineffective when applied to more established stages of dermal scarring. These combined findings demonstrate that relaxin provides a means to regulate excessive collagen deposition in disease states characterized by dermal fibrosis and with our previously published work demonstrate the relaxin-null mouse as a model of progressive scleroderma.

Relaxin is a key mediator of prostate growth and male reproductive tract development.

Male mice deficient in relaxin showed retarded growth and marked deficiencies in the reproductive tract within 1 month of age. At 3 months of age, male reproductive organ weight (including the testis, epididymis, prostate, and seminal vesicle) from relaxin null (RLX-/-) mice were significantly (p < 0.05) smaller than those of wild-type (RLX+/+) male mice. Histologic examination of RLX-/- mouse tissues demonstrated decreased sperm maturation (testis), increased collagen, and decreased epithelial proliferation in the prostate compared with tissues obtained from RLX+/+ animals. The degree of sperm maturation in the testes of sexually mature RLX-/- mice (3 months) resembled that of immature (1 month) RLX+/+ mice and correlated with a decrease in fertility in RLX-/- mice. The marked differences in the extracellular matrix of the testis and prostate in RLX-/- males also correlated with an increase in the rate of cell apoptosis. Relaxin and LGR7 (relaxin receptor) mRNA expression was demonstrated in the prostate gland and testis of the normal mouse. Data from this study demonstrate that relaxin is an important factor in the development and function of the male reproductive tract in mice and has an essential role in the growth of the prostate and maintenance of male fertility. Relaxin may mediate its effects on growth and development by serving as an antiapoptotic factor.