Data abstractions for decision tree induction

AbstractWhen descriptions of data values in a database are too concrete or too detailed, the computational complexity needed to discover useful knowledge from the database will be generally increased. Furthermore, discovered knowledge tends to become complicated. A notion of data abstraction seems useful to resolve this kind of problems, as we obtain a smaller and more general database after the abstraction, from which we can quickly extract more abstract knowledge that is expected to be easier to understand. In general, however, since there exist several possible abstractions, we have to carefully select one according to which the original database is generalized. An inadequate selection would make the accuracy of extracted knowledge worse.From this point of view, we propose in this paper a method of selecting an appropriate abstraction from possible ones, assuming that our task is to construct a decision tree from a relational database. Suppose that, for each attribute in a relational database, we have a class of possible abstractions for the attribute values. As an appropriate abstraction for each attribute, we prefer an abstraction such that, even after the abstraction, the distribution of target classes necessary to perform our classification task can be preserved within an acceptable error range given by user.By the selected abstractions, the original database can be transformed into a small generalized database written in abstract values. Therefore, it would be expected that, from the generalized database, we can construct a decision tree whose size is much smaller than one constructed from the original database. Furthermore, such a size reduction can be justified under some theoretical assumptions. The appropriateness of abstraction is precisely defined in terms of the standard information theory. Therefore, we call our abstraction framework Information Theoretical Abstraction.We show some experimental results obtained by a system ITA that is an implementation of our abstraction method. From those results, it is verified that our method is very effective in reducing the size of detected decision tree without making classification errors so worse

Decrease in seroprevalence of Hepatitis A after the implementation of nationwide disposable tableware use in Taiwan

<p>Abstract</p> <p>Background</p> <p>Taiwan is an endemic area of viral hepatitis, including hepatitis A, which is transmitted mainly from the fecal-oral route. In order to reduce the transmission through food intake, the government implemented a policy of nationwide disposal tableware use in public eating places in 1982. We conducted a study to estimate the seroprevalence of Hepatitis A in a group of workers in Taiwan in 2005, determine the risk factors, and compare seroprevalence to published estimates in Taiwan to evaluate changes in the seroprevalence after the implementation of the nationwide disposal tableware use.</p> <p>Methods</p> <p>We recruited workers of an industrial park during their annual health examinations in 2005 and measured their anti-hepatitis A virus IgG titer using microparticle enzyme immunoassay. We compared the seroprevalence across different birth cohorts within the study population and also analyzed data from previous studies.</p> <p>Results</p> <p>The overall sero-positive rate was 22.0% in the 11,777 participants. The rate was much lower among those who were covered by the program since birth (born after 1982) in comparison with those who were not (2.7% vs. 25.3%, p < 0.001). From the analyses of data from pervious studies, we found the age-specific rates were similar in cohorts born in or after 1982 across studies conducted in different time periods but decreased with the calendar year in cohorts born before 1982. In particular, the age-specific seroprevalence dropped to less than one third in a three-year period among those who were born around 1982.</p> <p>Conclusions</p> <p>Data from both the current and previous studies in different time periods supported the effectiveness of disposal tableware in preventing the transmission of hepatitis A.</p

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P &lt; 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification

Background: Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression signatures of early MI and subclinical atherosclerosis in the Framingham Heart Study (FHS). In this study, we conducted paired-end RNA sequencing on whole blood collected from 198 FHS participants (55 with a history of early MI, 72 with high CAC without prior MI, and 71 controls free of elevated CAC levels or history of MI). We applied DESeq2 to identify coding-genes and long intergenic noncoding RNAs (lincRNAs) differentially expressed in MI and high CAC, respectively, compared with the control. Results: On average, 150 million paired-end reads were obtained for each sample. At the false discovery rate (FDR) < 0.1, we found 68 coding genes and 2 lincRNAs that were differentially expressed in early MI versus controls. Among them, 60 coding genes were detectable and thus tested in an independent RNA-Seq data of 807 individuals from the Rotterdam Study, and 8 genes were supported by p value and direction of the effect. Immune response, lipid metabolic process, and interferon regulatory factor were enriched in these 68 genes. By contrast, only 3 coding genes and 1 lincRNA were differentially expressed in high CAC versus controls. APOD, encoding a component of high-density lipoprotein, was significantly downregulated in both early MI (FDR = 0.007) and high CAC (FDR = 0.01) compared with controls. Conclusions: We identified transcriptomic signatures of early MI that include differentially expressed protein-coding genes and lincRNAs, suggesting important roles for protein-coding genes and lincRNAs in the pathogenesis of MI

Democratic Leadership - A local story

Leadership is traditionally viewed as an individual property and researched from the perspective of behaviours, traits or characteristics that these individuals possess. Notions of democratic leadership can offer early childhood centres a more expansive conception of leadership to include children, teachers and families. This study explores the possibility of positioning all stakeholders in an early childhood centre as leaders by repositioning leadership as a jointly constructed, emergent process. Drawing on an existing feature of the kindergarten programme, that of regular excursions within the local community, connections are interwoven between children’s inquires, democratic principles and elements of place based education. Using narratives from five excursions in the local community the study experiments with Leadership-as-practice to analyse how these excursions fostered democratic and inclusive participation of children and adults. Inquiry as a form of participatory democracy is a key feature of decision-making and provides a common purpose for community excursions while encouraging leadership opportunities. The study reveals the potential of leadership-as-practice, underpinned by democratic values as an approach to leadership in early childhood organisations, enabling leader/follower roles to be blurred and learning to be co constructed during dialogue. The local community holds enormous capacity as a system to facilitate democratic leadership and promote place based learning and citizenship education. This study recognises that democratic leadership exists in tension with current neo liberal beliefs and therefore positions itself as a counter to the current market driven early childhood environment. The underlying belief of this study is that leadership can occur as a collaborative practice, emerging through day to day experiences and seeks to contribute to the slowly emerging body of research concerned with early childhood leadership.

Genome-wide association study for renal traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies

Background: The Framingham Heart Study (FHS) recently obtained initial results from the first genome-wide association scan for renal traits. The study of 70,987 single nucleotide polymorphisms (SNPs) in 1,010 FHS participants provides a list of SNPs showing the strongest associations with renal traits which need to be verified in independent study samples. Methods: Sixteen SNPs were selected for replication based on the most promising associations with chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and serum cystatin C in FHS. These SNPs were genotyped in 15,747 participants of the Atherosclerosis in Communities (ARIC) Study and evaluated for association using multivariable adjusted regression analyses. Primary outcomes in ARIC were CKD and eGFR. Secondary prospective analyses were conducted for association with kidney disease progression using multivariable adjusted Cox proportional hazards regression. The definition of the outcomes, all covariates, and the use of an additive genetic model was consistent with the original analyses in FHS. Results: The intronic SNP rs6495446 in the gene MTHFS was significantly associated with CKD among white ARIC participants at visit 4: the odds ratio per each C allele was 1.24 (95% CI 1.09–1.41, p = 0.001). Borderline significant associations of rs6495446 were observed with CKD at study visit 1 (p = 0.024), eGFR at study visits 1 (p = 0.073) and 4 (lower mean eGFR per C allele by 0.6 ml/min/1.73 $\text{m}^2$, p = 0.043) and kidney disease progression (hazard ratio 1.13 per each C allele, 95% CI 1.00–1.26, p = 0.041). Another SNP, rs3779748 in EYA1, was significantly associated with CKD at ARIC visit 1 (odds ratio per each T allele 1.22, p = 0.01), but only with eGFR and cystatin C in FHS. Conclusion: This genome-wide association study provides unbiased information implicating MTHFS as a candidate gene for kidney disease. Our findings highlight the importance of replication to identify common SNPs associated with renal traits

Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using $\sim$2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant $(p<5 \times 10^{-8})$ or suggestive associations $(p<4 \times 10^{-7})$ were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding $(p<4 \times 10^{-7})$. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels

Toll-Like Receptor 1 Locus Re-examined in a Genome-Wide Association Study Update on Anti–Helicobacter pylori IgG Titers

Funding Information: Funding The Rotterdam Study I-II was supported by the Netherlands Organization of Scientific Research (NWO; 175.010.2005.011, 911-03-012), Research Institute for Diseases in the Elderly (RIDE; 014-93-015), Genomics Initiative/NWO (project no. 050-060-810), Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), Ministry of Education, Culture, and Science and Ministry for Health, Welfare, and Sports, European Commission, and the Municipality of Rotterdam. GenerationR was supported by Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, ZonMw (907.00303, 916.10159), NWO, and the Ministry for Health, Welfare and Sports. The Study of Health in Pomerania (SHIP) and SHIP-TREND were supported by Deutsche Krebshilfe/Dr Mildred-Scheel-Stiftung (109102), Deutsche Forschungsgemeinschaft (DFG GRK840-D2/E3/E4, MA 4115/1-2/3), Federal Ministry of Education and Research (BMBF GANI-MED 03IS2061A and BMBF 0314107, 01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012), the European Union (EU-FP-7-EPCTM and EU-FP7-REGPOT-2010-1), AstraZeneca (unrestricted grant), the Federal Ministry of Education and Research, Siemens Healthcare, the Federal State of Mecklenburg–West Pomerania, and the University of Greifswald. The Framingham Heart Study was supported by National Institutes of Health grants N01-HC-25195, HHSN268201500001I, and 75N92019D00031 (to Boston University) and the Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI). The Multi-Ethnic Study of Atherosclerosis (MESA) and the MESA SHARe projects were supported by the NHLBI (75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420. Funding for SHARe genotyping was provided by NHLBI grant N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, CA) and the Broad Institute of Harvard and MIT (Boston, MA) using the Affymetrix Genome-Wide Human SNP Array 6.0. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Epidemiological Investigations on Chances of Preventing Recognizing Early and Optimally Treating Chronic Diseases in an Elderly Population were supported by the State Ministry of Science, Research and Arts, Baden-Württemberg, Federal Ministry of Education and Research, and Federal Ministry of Family Affairs, Senior Citizens, Women and Youth. LATVIA was supported by the European Regional Development Fund (ERDF; 009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016), National Program for Research in Latvia, Ministry of Health (6-1396-2016), and Fundamental and Applied Research Projects Program in Latvia (project no. lzp-2018/1-0135). Funding Information: Conceptualization: Linda Broer, Manon C.W. Spaander, Fabian Frost, Stefan Weiss, Georg Homuth, Henry Völzke, Markus M. Lerch, Ben Schöttker, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, Edmond K. Kabagambe, Marcis Leja, Janis Klovins, Raitis Peculis, Dace Rudzite, Liene Nikitina-Zake, Girts Skenders, Vita Rovite, André Uitterlinden, Ernst J. Kuipers, Maikel P. Peppelenbosch, and additional members of Rotterdam Study I-II, GenerationR, Study of Health in Pomerania, Framingham Heart Study, Multi-Ethnic Study of Atherosclerosis, Epidemiological Investigations on Chances of Preventing Recognizing Early and Optimally Treating Chronic Diseases in an Elderly Population, and LATVIA cohorts not directly involved in this manuscript. Methodology: all authors. Investigation: all authors. Formal analysis of discovery: Linda Broer, Fabian Frost, Stefan Weiss, Georg Homuth, Henry Völzke, Markus M. Lerch, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, and Edmond K. Kabagambe. Formal analysis of replication: Yan Zhang, Hannah Stocker, Hermann Brenner, Marcis Leja, Janis Klovins, and Raitis Peculis. Formal analysis of meta-analysis: Linda Broer. Project administration: Suk Yee Lam and Gwenny M. Fuhler. Resources: Fabian Frost, Stefan Weiss, Georg Homuth, Henry Völzke, Markus M. Lerch, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, Edmond K. Kabagambe, Marcis Leja, Janis Klovins, Dace Rudzite, Liene Nikitina-Zake, Girts Skenders, Vita Rovite, Ernst J. Kuipers, and Maikel P. Peppelenbosch. Supervision: Manon C.W. Spaander, Fabian Frost, Stefan Weiss, Georg Homuth, Henry Völzke, Markus M. Lerch, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C. Wood, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russell P. Tracy, Edmond K. Kabagambe, Marcis Leja, Janis Klovins, Gwenny M. Fuhler, Maikel P. Peppelenbosch, and André Uitterlinden. Visualization: Suk Yee Lam, Michiel C. Mommersteeg, Bingting Yu, Linda Broer, and Gwenny M. Fuhler. Writing—original draft: Suk Yee Lam, Michiel C. Mommersteeg, and Gwenny M. Fuhler. Writing—reviewing and editing: all authors. Publisher Copyright: © 2022 The Author(s)Background & Aims: A genome-wide significant association between anti–Helicobacter pylori (H pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigated this association in an updated genome-wide association study (GWAS) meta-analysis for populations with low gastric cancer incidence, address potential causes of cohort heterogeneity, and explore functional implications of genetic variation at the TLR1/6/10 locus. Methods: The dichotomous GWAS (25% individuals exhibiting highest anti–H pylori IgG titers vs remaining 75%) included discovery and replication sampls of, respectively, n = 15,685 and n = 9676, all of European ancestry. Longitudinal analysis of serologic data was performed on H pylori–eradicated subjects (n = 132) and patients under surveillance for premalignant gastric lesions (n = 107). TLR1/6/10 surface expression, TLR1 mRNA, and cytokine levels were measured in leukocyte subsets of healthy subjects (n = 26) genotyped for TLR1/6/10 variants. Results: The association of the TLR1/6/10 locus with anti–H pylori IgG titers (rs12233670; β = −0.267 ± SE 0.034; P = 4.42 × 10−15) presented with high heterogeneity and failed replication. Anti–H pylori IgG titers declined within 2–4 years after eradication treatment (P = 0.004), and decreased over time in patients with premalignant gastric lesions (P < 0.001). Variation at the TLR1/6/10 locus affected TLR1-mediated cytokine production and TLR1 surface expression on monocytes (P = 0.016) and neutrophils (P = 0.030), but not mRNA levels. Conclusions: The association between anti–H pylori IgG titers and TLR1/6/10 locus was not replicated across cohorts, possibly owing to dependency of anti–H pylori IgG titers on therapy, clearance, and antibody decay. H pylori–mediated immune cell activation is partly mediated via TLR1 signaling, which in turn is affected by genetic variation.publishersversionPeer reviewe

Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes

BACKGROUND:Cardiovascular disease (CVD) and its most common manifestations - including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) - are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes.METHODS:In 1345 Framingham Heart Study participants from the largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118; myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency [greater than or equal to]0.10, genotype call rate [greater than or equal to]0.80, and Hardy-Weinberg equilibrium p-value [greater than or equal to] 0.001.RESULTS:Six associations yielded p <10-5. The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 x 10-6; major CHD, rs2549513, p = 9.7 x 10-6; AF, rs958546, p = 4.8 x 10-6; HF: rs740363, p = 8.8 x 10-6. Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD (p 1.7 - 1.9 x 10-5) and major CHD (p 2.5 - 3.5 x 10-4) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 x 10-6) and HF (p = 1.2 x 10-4). Complete results for these phenotypes can be found at the dbgap website http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies

Association of Estimated Glomerular Filtration Rate and Urinary Uromodulin Concentrations with Rare Variants Identified by UMOD Gene Region Sequencing

Background: Recent genome-wide association studies (GWAS) have identified common variants in the UMOD region associated with kidney function and disease in the general population. To identify novel rare variants as well as common variants that may account for this GWAS signal, the exons and 4 kb upstream region of UMOD were sequenced. Methodology/Principal Findings Individuals (n = 485) were selected based on presence of the GWAS risk haplotype and chronic kidney disease (CKD) in the ARIC Study and on the extremes of of the UMOD gene product, uromodulin, in urine (Tamm Horsfall protein, THP) in the Framingham Heart Study (FHS). Targeted sequencing was conducted using capillary based Sanger sequencing (3730 DNA Analyzer). Variants were tested for association with THP concentrations and estimated glomerular filtration rate (eGFR), and identified non-synonymous coding variants were genotyped in up to 22,546 follow-up samples. Twenty-four and 63 variants were identified in the 285 ARIC and 200 FHS participants, respectively. In both studies combined, there were 33 common and 54 rare (MAF<0.05) variants. Five non-synonymous rare variants were identified in FHS; borderline enrichment of rare variants was found in the extremes of THP (SKAT p-value = 0.08). Only V458L was associated with THP in the FHS general-population validation sample (p = 9*10$^{−3}$, n = 2,522), but did not show direction-consistent and significant association with eGFR in both the ARIC (n = 14,635) and FHS (n = 7,520) validation samples. Pooling all non-synonymous rare variants except V458L together showed non-significant associations with THP and eGFR in the FHS validation sample. Functional studies of V458L revealed no alternations in protein trafficking. Conclusions/Significance: Multiple novel rare variants in the UMOD region were identified, but none were consistently associated with eGFR in two independent study samples. Only V458L had modest association with THP levels in the general population and thus could not account for the observed GWAS signal