MEGADOCK 3.0: a high-performance protein-protein interaction prediction software using hybrid parallel computing for petascale supercomputing environments

BACKGROUND: Protein-protein interaction (PPI) plays a core role in cellular functions. Massively parallel supercomputing systems have been actively developed over the past few years, which enable large-scale biological problems to be solved, such as PPI network prediction based on tertiary structures. RESULTS: We have developed a high throughput and ultra-fast PPI prediction system based on rigid docking, “MEGADOCK”, by employing a hybrid parallelization (MPI/OpenMP) technique assuming usages on massively parallel supercomputing systems. MEGADOCK displays significantly faster processing speed in the rigid-body docking process that leads to full utilization of protein tertiary structural data for large-scale and network-level problems in systems biology. Moreover, the system was scalable as shown by measurements carried out on two supercomputing environments. We then conducted prediction of biological PPI networks using the post-docking analysis. CONCLUSIONS: We present a new protein-protein docking engine aimed at exhaustive docking of mega-order numbers of protein pairs. The system was shown to be scalable by running on thousands of nodes. The software package is available at: http://www.bi.cs.titech.ac.jp/megadock/k/

Regioselective glucosidation of trans-resveratrol in Escherichia coli expressing glucosyltransferase from Phytolacca americana

A glucosyltransferase (GT) of Phytolacca americana (PaGT3) was expressed in Escherichia coli and purified for the synthesis of two O-β-glucoside products of trans-resveratrol. The reaction was moderately regioselective with a ratio of 4′-O-β-glucoside: 3-O-β-glucoside at 10:3. We used not only the purified enzyme but also the E. coli cells containing the PaGT3 gene for the synthesis of glycoconjugates. E. coli cell cultures also have other advantages, such as a shorter incubation time compared with cultured plant cells, no need for the addition of exogenous glucosyl donor compounds such as UDP-glucose, and almost complete conversion of the aglycone to the glucoside products. Furthermore, a homology model of PaGT3 and mutagenesis studies suggested that His-20 would be a catalytically important residue

Degenerative changes in the appendicular joints of ancient human populations from the Japan Islands

Degenerative changes in six major limb joints were investigated to compare their prevalence among five ancient skeletal populations from the Japan Islands. The populations assessed in this study consisted of the farmers in the northern Kyushu/Yamaguchi area and the foragers from the northwestern Kyushu area from the Yayoi period (5th century BC to 3rd century AD); the Okhotsk (5th to 12th centuries AD) foragers from Hokkaido and Sakhalin; the common people from medieval Kamakura (12th to 14th centuries AD) in Kanto, central Japan; and the early-modern farmers (17th to 19th centuries AD) from Kumejima, in the southernmost island chain (Ryukyu Islands). Crude prevalence comparisons showed that the shoulder and hip joints were principally affected in early-modern Kumejima and medieval Kamakura, which contrasted with the high prevalence of elbow and knee joint changes in the Okhotsk people. The heavy dependence on marine mammals and fish for dietary protein intake probably required flexion and extension movements of the most severely degenerated joints in the Okhotsk people. The northern Kyushu/Yamaguchi and northwestern Kyushu Yayoi peoples were more affected by degeneration in the wrist joints than others, possibly due to their use of innovative tools such as stone or shell knives and harpoons. A multivariate logistic regression analysis, adjusted for age, region, and sex as the predictor variables for degenerative changes in joints, was applied to only the two samples from Kumejima and Kamakura (including previously reported spine data) because of their better preservation. This revealed differences in the prevalence of changes in some joints; for example, age-related changes were recognized. The Kumejima people were more commonly affected by hip and knee joint changes, whereas the Kamakura people were more commonly affected by changes to apophyseal joints. Because a stable isotope analysis indicated that the trophic levels of the two populations were almost the same, the pattern of degenerative changes would have reflected differences in their specific workloads, such as wet rice cultivation using a peculiar hoe by the Kumejima people. This study, combining multivariate logistic regression analysis of degenerative joint changes and stable isotope analyses, uses large skeletal populations to add clarity to the actual rigors of ancient life. © 2015 Elsevier Ltd and INQUA

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

A case report of primary sternal osteomyelitis caused by polymicrobial bacteria, including Actinomyces israelii

We herein report a case of primary sternal osteomyelitis caused by polymicrobial bacteria, including Actinomyces israelii. A 72-year-old man presented with a fever and precordial pain. Chest computed tomography (CT) revealed peristernal fluid associated with an osteolytic lesion and a peripheral nodule in the right upper lobe. We suspected sternal osteomyelitis, and an incision and drainage were performed. Culture of the drainage fluid and bone tissue yielded A. israelii, Fusobacterium necrophorum, and Streptococcus constellatus. Treatment with benzylpenicillin potassium (PCG) was administered. A subsequent chest CT scan showed that the peripheral nodule decreased in size after antimicrobial therapy. We therefore presumed the peripheral nodule as septic pulmonary embolism(SPE). Antimicrobial agents were administered for a total of 6 months. To our knowledge, this is the first case report of primary sternal osteomyelitis associated with presumed SPE caused by polymicrobial bacteria, including A. israelii. It is important to identify the causative pathogen in osteomyelitis, which requires long-term antibiotic treatment