Periodicity of SNP distribution around transcription start sites

BACKGROUND: Several millions single nucleotide polymorphisms (SNPs) have already been collected and deposited in public databases and these are important resources not only for use as markers to identify disease-associated genes, but also to understand the mechanisms that underlie the genome diversification. RESULTS: A spectrum analysis of SNP density distribution in the genomic regions around transcription start sites (TSSs) revealed a remarkable periodicity of 146 nucleotides. This periodicity was observed in the regions that were associated with CpG islands (CGIs), but not in the regions without CpG islands (nonCGIs). An analysis of the sequence divergence of the same genomic regions between humans and chimpanzees also revealed a similar periodical pattern in CGI. The occurrences of any mono- or di-nucleotide sequences in these regions did not reveal such a periodicity, thus indicating that an interpretation of this periodicity solely based on the sequence-dependent susceptibility to mutation is highly unlikely. CONCLUSION: The periodical patterns of nucleotide variability suggest the location of nucleosomes that are phased at TSS, and can be viewed as the genetic footprint of the chromatin state that has been maintained throughout mammalian evolutionary history. The results suggest the possible involvement of the nucleosome structure in the promoter function, and also a fundamental functional/structural difference between the two promoter classes, i.e., those with and without CGIs

Evaluation of Haplotype Inference Using Definitive Haplotype Data Obtained from Complete Hydatidiform Moles, and Its Significance for the Analyses of Positively Selected Regions

The haplotype map constructed by the HapMap Project is a valuable resource in the genetic studies of disease genes, population structure, and evolution. In the Project, Caucasian and African haplotypes are fairly accurately inferred, based mainly on the rules of Mendelian inheritance using the genotypes of trios. However, the Asian haplotypes are inferred from the genotypes of unrelated individuals based on population genetics, and are less accurate. Thus, the effects of this inaccuracy on downstream analyses needs to be assessed. We determined true Japanese haplotypes by genotyping 100 complete hydatidiform moles (CHM), each carrying a genome derived from a single sperm, using Affymetrix 500 K Arrays. We then assessed how inferred haplotypes can differ from true haplotypes, by phasing pseudo-individualized true haplotypes using the programs PHASE, fastPHASE, and Beagle. We found that, at various genomic regions, especially the MHC locus, the expansion of extended haplotype homozygosity (EHH), which is a measure of positive selection, is obscured when inferred Asian haplotype data is used to detect the expansion. We then mapped the genome using a new statistic, XDiHH, which directly detects the difference between the true and inferred haplotypes, in the determination of EHH expansion. We also show that the true haplotype data presented here is useful to assess and improve the accuracy of phasing of Asian genotypes

Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data

Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data

Variables that influence the maintenance of exclusive breastfeeding

Pesquisa descritiva, exploratória e retrospectiva, com abordagem quantitativa, realizada em uma comunidade carente de São Paulo com o objetivo de verificar se a manutenção do aleitamento exclusivo (AE) nos primeiros seis meses é influenciada pelas variáveis: contato precoce na primeira hora após o nascimento, permanência em alojamento conjunto, tipo de parto e tipo de hospital. Os dados foram coletados de 75 prontuários e analisados com a metodologia de equações de estimação generalizada. Os resultados mostraram que as variáveis alojamento conjunto, tipo de hospital e tipo de parto interferiram na manutenção do AE, o mesmo não ocorrendo com o contato precoce. Concluiu-se que os índices de AE foram maiores nos casos em que mãe e bebê permaneceram constantemente juntos após o parto, em hospitais amigos da criança e após partos normais. Constatou-se que a assistência recebida pela mulher durante o processo de parto e nascimento influencia de forma direta a amamentação.Se trata de una investigación descriptiva, exploratoria y retrospectiva, con abordaje cuantitativo, realizada en una comunidad carente de San Pablo, con el objetivo de verificar si la manutención del amamantar exclusivo (AE) en los primeros seis meses fue influenciada por las variables: contacto precoz en la primera hora después del nacimiento, permanencia en el mismo alojamiento, tipo de parto y tipo de hospital. Los datos fueron recolectados de 75 registros y analizados con la metodología de ecuaciones de cálculo generalizado. Los resultados mostraron que las variables alojamiento conjunto, tipo de hospital y tipo de parto interfirieron en la manutención del AE, lo mismo no ocurrió con el contacto precoz. Se concluye que los índices de AE fueron mayores en los casos en que la madre y el bebé permanecieron constantemente juntos después del parto, en hospitales amigos del niño y después de partos normales. Se constató que la asistencia recibida por la mujer durante el proceso de parto y nacimiento influye de forma directa en el amamantar.This is a descriptive, exploratory and retrospective study, with a quantitative approach, performed in a low-income community in São Paulo, with the purpose to identify whether the maintenance of exclusive breastfeeding (EBF) in the first six months is influenced by the following variables: early contact in the first hour after birth, permanence in joint lodging, type of delivery and type of hospital. Data were collected from 75 medical records and analyzed with the methodology of generalized estimate equations. The results showed that the variables joint lodging, type of hospital and type of delivery interfered in the maintenance of EBF; however, that was not the case with early contact. It was concluded that the EBF indexes were higher in cases where the mother and the baby remained together after the birth, in baby-friendly hospitals and after normal deliveries. It was also observed that the care received by the mother during the process of delivery and birth influences breastfeeding directly

PDK2 leads to cisplatin resistance through suppression of mitochondrial function in ovarian clear cell carcinoma

Ovarian clear cell carcinoma (CCC) exhibits an association with endometriosis, resistance to oxidative stress, and poor prognosis owing to its resistance to conventional platinum-based chemotherapy. A greater understanding of the molecular characteristics and pathogenesis of ovarian cancer subtypes may facilitate the development of targeted therapeutic strategies, though the mechanism of drug resistance in ovarian CCC has yet to be determined. In this study, we assessed exome sequencing data to identify new therapeutic targets of mitochondrial function in ovarian CCC because of the central role of mitochondria in redox homeostasis. Copy number analyses revealed that chromosome 17q21-24 (chr.17q21-24) amplification was associated with recurrence in ovarian CCC. Cell viability assays identified an association between cisplatin resistance and chr.17q21-24 amplification, and mitochondrion-related genes were enriched in patients with chr.17q21-24 amplification. Patients with high expression of pyruvate dehydrogenase kinase 2 (PDK2) had a worse prognosis than those with low PDK2 expression. Furthermore, inhibition of PDK2 synergistically enhanced cisplatin sensitivity by activating the electron transport chain and by increasing the production of mitochondrial reactive oxygen species. Mouse xenograft models showed that inhibition of PDK2 with cisplatin inhibited tumor growth. This evidence suggests that targeting mitochondrial metabolism and redox homeostasis is an attractive therapeutic strategy for improving drug sensitivity in ovarian CCC

A Specification Method of Character String Region in Augmented Reality

This paper proposes a method to enter characters and/or character string in an augmented reality using a gesture motion. The proposed method detects the region of character string using the gesture motion. It consists of five phases; template generation, skin color detection, hand region detection, gesture motion extraction and designation of character string region. The template image consists of two fingers because a gesture is to take hold the tips of the first and second fingers. In the skin color detection, we extract the skin color on the basis of values in saturation by using threshold processing. The hand region is detected by calculating areas and detecting the area with the maximum value as a hand. The gesture motion is extracted using template matching. In order to show the effectiveness of the proposed method, we conduct experiments for character string specification

Dysbiosis of the gut microbiota as a susceptibility factor for Kawasaki disease

IntroductionGut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD. MethodsFecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.ResultsFor alpha diversity, Faith’s phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray–Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini–Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of Ruminococcus gnavus group and lower relative abundance of Blautia. Discussion and conclusionRuminococcus gnavus group reportedly includes pro-inflammatory bacteria. In contrast, Blautia suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of Blautia in parallel with increased abundance of Ruminococcus gnavus group might be a susceptibility factor for KD

Raman Fingerprints of SARS-CoV‐2 Omicron Subvariants: Molecular Roots of Virological Characteristics and Evolutionary Directions

The latest RNA genomic mutation of SARS-CoV-2 virus, termed the Omicron variant, has generated a stream of highly contagious and antibody-resistant strains, which in turn led to classifying Omicron as a variant of concern. We systematically collected Raman spectra from six Omicron subvariants available in Japan (i.e., BA.1.18, BA.2, BA.4, BA.5, XE, and BA.2.75) and applied machinelearning algorithms to decrypt their structural characteristics at the molecular scale. Unique Raman fingerprints of sulfur-containing amino acid rotamers, RNA purines and pyrimidines, tyrosine phenol ring configurations, and secondary protein structures clearly differentiated the six Omicron subvariants. These spectral characteristics, which were linked to infectiousness, transmissibility, and propensity for immune evasion, revealed evolutionary motifs to be compared with the outputs of genomic studies. The availability of a Raman “metabolomic snapshot”, which was then translated into a barcode to enable a prompt subvariant identification, opened the way to rationalize in real-time SARS-CoV-2 activity and variability. As a proof of concept, we applied the Raman barcode procedure to a nasal swab sample retrieved from a SARS-CoV-2 patient and identified its Omicron subvariant by coupling a commercially available magnetic bead technology with our newly developed Raman analyses