Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment

Earthquake-induced prompt gravity signals identified in dense array data in Japan

Abstract Earthquake ruptures cause mass redistribution, which is expected to induce transient gravity perturbations simultaneously at all distances from the source before the arrival of P-waves. A recent research paper reported the detection of such prompt gravity signals from the 2011 Tohoku-Oki earthquake by comparing observed acceleration waveforms and model simulations. The 11 observed waveforms presented in that paper recorded in East Asia shared a similar trend above the background seismic noise and were in good agreement with the simulations. However, the signal detection was less quantitative because the significance of the observed signals was not discussed and the waveforms at other stations in the region were not shown. In this study, similar trends were not observed in most of the data recorded near the stations used in the aforementioned study, suggesting that the reported signals were only local noises. We thus took a different approach to identify the prompt signals. We optimized the multi-channel data recorded by superconducting gravimeters, broadband seismometers, and tiltmeters. Though no signal was identified in the single-trace records, the stacked trace of the broadband seismometer array data in Japan showed a clear signal above the reduced noise level. The signal amplitude was 0.25 nm/s2 for an average distance of 987 km from the event hypocenter. This detection was confirmed with a statistical significance of $$7\sigma$$ 7σ , where $$\sigma$$ σ is the standard deviation of the amplitude of the background noise. This result provided the first constraint on the amplitude of the observed prompt signals and may serve as a reference in the detection of prompt signals in future earthquakes

Development and Validation of a Data-Based Food Frequency Questionnaire for Adults in Eastern Rural Area of Rwanda

This study aimed to develop and evaluate the validity of a food frequency questionnaire (FFQ) for rural Rwandans. Since our FFQ was developed to assess malnutrition, it measured energy, protein, vitamin A, and iron intakes only. We collected 260 weighed food records (WFRs) from a total of 162 Rwandans. Based on the WFR data, we developed a tentative FFQ and examined the food list by percent contribution to energy and nutrient intakes. To assess the validity, nutrient intakes estimated from the FFQ were compared with those calculated from three-day WFRs by correlation coefficient and cross-classification for 17 adults. Cumulative contributions of the 18-item FFQ to the total intakes of energy and nutrients reached nearly 100%. Crude and energy-adjusted correlation coefficients ranged from -0.09 (vitamin A) to 0.58 (protein) and from -0.19 (vitamin A) to 0.68 (iron), respectively. About 50%-60% of the participants were classified into the same tertile. Our FFQ provided acceptable validity for energy and iron intakes and could rank Rwandan adults in eastern rural area correctly according to their energy and iron intakes