Multi-omics integration reveals molecular networks and regulators of psoriasis.

BackgroundPsoriasis is a complex multi-factorial disease, involving both genetic susceptibilities and environmental triggers. Genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) have been carried out to identify genetic and epigenetic variants that are associated with psoriasis. However, these loci cannot fully explain the disease pathogenesis.MethodsTo achieve a comprehensive mechanistic understanding of psoriasis, we conducted a systems biology study, integrating multi-omics datasets including GWAS, EWAS, tissue-specific transcriptome, expression quantitative trait loci (eQTLs), gene networks, and biological pathways to identify the key genes, processes, and networks that are genetically and epigenetically associated with psoriasis risk.ResultsThis integrative genomics study identified both well-characterized (e.g., the IL17 pathway in both GWAS and EWAS) and novel biological processes (e.g., the branched chain amino acid catabolism process in GWAS and the platelet and coagulation pathway in EWAS) involved in psoriasis. Finally, by utilizing tissue-specific gene regulatory networks, we unraveled the interactions among the psoriasis-associated genes and pathways in a tissue-specific manner and detected potential key regulatory genes in the psoriasis networks.ConclusionsThe integration and convergence of multi-omics signals provide deeper and comprehensive insights into the biological mechanisms associated with psoriasis susceptibility

Molecular genetic characterization of a pathogenicity-attenuated mutant of Pseudomonas syringae pathovar syringae

A pathogenicity locus of Pseudomonas syringae pv. syringae identified by Tn5 mutagenesis was investigated. The mutant strain PS9024 is attenuated for disease expression in its host, Phaseolus vulgaris, but produces the hypersensitive reaction (HR) in the nonhost, tobacco (Nicotina tabacum). A cosmid clone carrying 16 kilobases (kb) of contiguous genomic DNA partially complements this mutant. Altered growth of the mutant in planta was also partially restored. Marker exchange mutagenesis with Tn3- HoHo1 at two other sites within this locus results in mutants with attenuated and severely reduced pathogenicity. The locus is complex and contains repetitive DNA sequences. Northern analysis reveals that this locus is expressed in planta, but is not expressed in a rich growth medium, and the transcript is larger than 10 kb, suggesting that the locus is transcribed as a polycistronic mRNA. Comparison of total cellular protein profiles of R32 and PS9024 using SDS-PAGE analysis further reveals that at least nine protein bands ranging from approximately 100 kD or above in size are present in the wild type strain R32, but absent from the mutant. Additionally, a protein of approximately 45 kD is absent from the mutant. The site of Tn5 insertion has been partially sequenced. The initial search of the data banks suggested a gene or genes related to the ornithine biosynthetic pathway map to this locus. Further study strongly suggest a gene that encodes a membranceassociated protein and under the control of a promoter identical to appA gene promoter maps at this site and it is involved in the process of pathogenesis

Analysis of optical absorption in GaAs nanowire arrays

In this study, the influence of the geometric parameters on the optical absorption of gallium arsenide [GaAs] nanowire arrays [NWAs] has been systematically analyzed using finite-difference time-domain simulations. The calculations reveal that the optical absorption is sensitive to the geometric parameters such as diameter [D], length [L], and filling ratio [D/P], and more efficient light absorption can be obtained in GaAs NWAs than in thin films with the same thickness due to the combined effects of intrinsic antireflection and efficient excitation of resonant modes. Optimized geometric parameters are obtained as follows: D = 180 nm, L = 2 μm, and D/P = 0.5. Meanwhile, the simulation on the absorption of GaAs NWAs for oblique incidence has also been carried out. The underlying physics is discussed in this work