Log10p Values Research Articles

Increased serum CA724 levels in patients suffering gout vs cancers.

CA724 is a clinically used serum biomarker used for cancer diagnosis, which includes digestive tract cancers (esophageal, gastric, and colorectal carcinomas), ovarian cancer, and nonsmall cell lung cancer. In general, the serum CA724 level is lower than 6U/mL in healthy controls and significantly higher in cancer patients. It has been further established that serum CA724 level is related to the pathological stage and prognosis of cancers. However, CA724 is not only expressed in tumor tissues but also in normal tissues such as the secretory endometrium and transitional colonic mucosa, which indicates that CA724 is not a unique product of cancer cells. Currently, the serum CA724 levels in patients suffering cancer or nonneoplasm diseases have not been systematically measured and compared. In our study, a total of 38,526 clinical lab test results of serum CA724 levels from healthy controls and patients suffering 34 different types of diseases including cancers and nonneoplasm illnesses during the past 3 years (2015-2018) were collected and analyzed. We found that the mean values of serum CA724 levels were significantly higher in patients suffering gout (23.7U/mL) and gouty arthritis (31.45U/mL) than that of cancer patients (Mann-Whitney test, p<0.0001). The summarized mean and median values of serum CA724 data for healthy controls vs patients suffering 34 different types of diseases indicated that the abnormal serum CA724 levels might be a systemic malfunction indicator rather than a cancer cell-secreted product; the log10p values showed that CA724 is not only a cancer biomarker but also a potential biomarker for patients suffering gout.

Genome Wide Association Study Identifies New Loci Associated with Undesired Coat Color Phenotypes in Saanen Goats.

This paper reports a quantitative genetics and genomic analysis of undesirable coat color patterns in goats. Two undesirable coat colors have routinely been recorded for the past 15 years in French Saanen goats. One fifth of Saanen females have been phenotyped “pink” (8.0%) or “pink neck” (11.5%) and consequently have not been included in the breeding program as elite animals. Heritability of the binary “pink” and “pink neck” phenotype, estimated from 103,443 females was 0.26 for “pink” and 0.21 for “pink neck”. Genome wide association studies (using haplotypes or single SNPs) were implemented using a daughter design of 810 Saanen goats sired by 9 Artificial Insemination bucks genotyped with the goatSNP50 chip. A highly significant signal (-log10pvalue = 10.2) was associated with the “pink neck” phenotype on chromosome 11, suggesting the presence of a major gene. Highly significant signals for the “pink” phenotype were found on chromosomes 5 and 13 (-log10p values of 7.2 and, 7.7 respectively). The most significant SNP on chromosome 13 was in the ASIP gene region, well known for its association with coat color phenotypes. Nine significant signals were also found for both traits. The highest signal for each trait was detected by both single SNP and haplotype approaches, whereas the smaller signals were not consistently detected by the two methods. Altogether these results demonstrated a strong genetic control of the “pink” and “pink neck” phenotypes in French Saanen goats suggesting that SNP information could be used to identify and remove undesired colored animals from the breeding program.

Identification of novel loci associated with gastrointestinal parasite resistance in a Red Maasai x Dorper backcross population.

Gastrointestinal (GI) parasitic infection is the main health constraint for small ruminant production, causing loss of weight and/or death. Red Maasai sheep have adapted to a tropical environment where extreme parasite exposure is a constant, especially with highly pathogenic Haemonchus contortus. This breed has been reported to be resistant to gastrointestinal parasite infection, hence it is considered an invaluable resource to study associations between host genetics and resistance. The aim of this study was to identify polymorphisms strongly associated with host resistance in a double backcross population derived from Red Maasai and Dorper sheep using a SNP-based GWAS analysis. The animals that were genotyped represented the most resistant and susceptible individuals based on the tails of phenotypic distribution (10% each) for average faecal egg counts (AVFEC). AVFEC, packed cell volume (AVPCV), and live weight (AVLWT) were adjusted for fixed effects and co-variables, and an association analysis was run using EMMAX. Revised significance levels were calculated using 100,000 permutation tests. The top five significant SNP markers with - log10 p-values >3.794 were observed on five different chromosomes for AVFEC, and BLUPPf90/PostGSf90 results confirmed EMMAX significant regions for this trait. One of these regions included a cluster of significant SNP on chromosome (Chr) 6 not in linkage disequilibrium to each other. This genomic location contains annotated genes involved in cytokine signalling, haemostasis and mucus biosynthesis. Only one association detected on Chr 7 was significant for both AVPCV and AVLWT. The results generated here reveal candidate immune variants for genes involved in differential response to infection and provide additional SNP marker information that has potential to aid selection of resistance to gastrointestinal parasites in sheep of a similar genetic background to the double backcross population.

Equations for the Partition of Neutral Molecules, Ions and Ionic Species from Water to Water–Ethanol Mixtures

Equations set up for the transfer of neutral solutes from water to water–ethanol mixtures can also be used to correlate the transfer of ions and ionic species, as log10P, where P is the partition coefficient. Only two additional terms are required in the equations, one for anions and one for cations. The extended equations can fit log10P values for anions and cations with a standard deviation of about 0.2 to 0.3 log units for transfer of 41 anions and cations from water to various water–ethanol mixtures from 10 % ethanol to 100 % ethanol by volume. The log10P values for carboxylate anions and protonated amine cations as obtained from the variation of pKa with solvent are quite compatible with log10P values for simple anions and cations.

Genomic regions associated with bovine milk fatty acids in both summer and winter milk samples

BackgroundIn this study we perform a genome-wide association study (GWAS) for bovine milk fatty acids from summer milk samples. This study replicates a previous study where we performed a GWAS for bovine milk fatty acids based on winter milk samples from the same population. Fatty acids from summer and winter milk are genetically similar traits and we therefore compare the regions detected in summer milk to the regions previously detected in winter milk GWAS to discover regions that explain genetic variation in both summer and winter milk.ResultsThe GWAS of summer milk samples resulted in 51 regions associated with one or more milk fatty acids. Results are in agreement with most associations that were previously detected in a GWAS of fatty acids from winter milk samples, including eight ‘new’ regions that were not considered in the individual studies. The high correlation between the –log10(P-values) and effects of SNPs that were found significant in both GWAS imply that the effects of the SNPs were similar on winter and summer milk fatty acids.ConclusionsThe GWAS of fatty acids based on summer milk samples was in agreement with most of the associations detected in the GWAS of fatty acids based on winter milk samples. Associations that were in agreement between both GWAS are more likely to be involved in fatty acid synthesis compared to regions detected in only one GWAS and are therefore worthwhile to pursue in fine-mapping studies.

Abraham Model Correlations for Transfer of Neutral Molecules to Tetrahydrofuran and to 1,4-Dioxane, and for Transfer of Ions to Tetrahydrofuran

Data have been compiled from the published literature for the partition coefficients of solutes and vapors into anhydrous tetrahydrofuran and 1,4-dioxane. The logarithms of the water-to-ether partition coefficients, log10P, and gas-to-ether partition coefficients, log10K, were correlated with the Abraham solvation parameter model. The derived correlations described the observed log10P and log10K values for both ether solvents to within average standard deviations of 0.16 log10 units or less. The log10P correlation for tetrahydrofuran was extended to include the partition of ions by inclusion of a cation-solvent and an anion-solvent term.

Abstract 3764: Genome-wide association study identifies potential susceptibility loci associated with differential response to environmental insults in sporadic Chinese CRC patients

Abstract To date, genome-wide association studies (GWAS) have identified fourteen SNPs that influence risk of developing colorectal cancer (CRC) in Caucasians. None of these tagging SNPs is within coding region of a candidate gene. Only five of these SNPs were associated with CRC risk in Chinese population. We aimed to perform GWAS to identify new susceptibility loci associated with differential response to environmental insults in sporadic Chinese CRC patients. A total of 1,000 cases (aged 50 years or more) and 1,000 age- and gender-matched healthy controls were genotyped with Affymetrix SNP 6 array, a newer microarray platform which includes the ability to interrogate structural variants. Over 90% of the arrays have call rate of 99% or more. Thirty five arrays with call rate less than 97% and either null QC or negative QC (enzyme) values were replicated. Principal component analysis performed together with 270 HapMap and 92 Singapore Genome Variant Project (SGVP) samples indicate that there is no population substructure. Sixteen outliers were removed. SNPs with call rate less than 99% and minor allelic frequency less than 0.1, and control SNPs not in Hardy-Weinburg equilibrium were filtered. Subsequent quantile-quantile plot shows no evidence of allelic test statistic inflation. Twelve new chromosomal regions with SNPs having -log10 p-values greater than four and good clustering patterns were identified via Manhattan plot. Linkage disequilibrium (LD) analysis was performed to ascertain the LD blocks around these SNPs. SNPs in three chromosomal regions within the vicinity of promising CRC candidate genes were prioritized and currently being validated in a replication panel consisting of another 2,000 cases and controls. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3764. doi:10.1158/1538-7445.AM2011-3764

IGenomicViewer, a Gynecologic Oncology Group software library for the creation of highly customizable, portable, interactive, and linked visualizations of high throughput genomic data

e16544 Background: An R software library was created with the goal of creating customizable, platform independent, and portable visualization tools for the annotation, dissemination and interrogation of high dimensioned genomic data. Methods: A set of R functions were created to extend the functionality of the sendplot R library. The functions were applied to BAC aCGH data generated for several GOG studies. Results: The iGenomicViewer function calls created and populated a directory structure which was then ported to a password protected server for interrogation by research team members. The linked html and image output allows users to examine genome wide plots of aberration frequencies and p-values and then drill down to visualizations of regions of interest. Users can interrogate a panel of plots which includes: 1) a heat map of the aCGH data for with tool-tip display of sample and assay specific data (e.g., assay values, sample IDs, and hyperlinks to UCSC browser and sample specific images); 2) a set of interactive annotation tracks which display location of cancer, disease and DNA repair genes; and 3) a plot which displays -log10 p-values and/or aberration frequencies for the BAC assays depicted in the heatmap. For the smallest regions of interest, the panel of plots contains a tiled heatmap which depicts the overlap and gaps in BAC coverage and their alignment with the gene locations represented in the adjacent annotation track. Conclusions: The iGenomicViewer library provides open source software for creation of customizable visualization tools for collaborative research projects involving high dimensioned genomic data. No significant financial relationships to disclose.

Exploration of the Genetic Basis of GVHD by Genetic Association Studies

Graft-versus-host disease (GVHD), as well as graft-versus-leukemia effect (GVL), are essentially allo-immune reactions, which are induced by the engrafted donor T cells that recognize the host-derived allo-antigens presented on their targets (Figure 1). In HLA-matched transplantation, these antigens are called minor histocompatibility antigens (mHags), and are typically defined by the host single nucleotide polymorphisms (SNPs) that are not shared by the donor and therefore considered to be genetically mismatched between the donor and the recipient [1–3]. Thus, the development of both allo-reactions absolutely depends on the presence of 1 or more mismatched mHags, although these reactions could be further modified by other genetic as well as environmental factors, including, cytokine polymorphisms and GVHD prophylaxis. So, in view of better preventing GVHD and specifically targeting allo-immunity to the tumor component, central questions are what mHAgs are responsible for the development of GVHD or GVL and what genetic factors can influence the overall reactions, which are the plausible targets of genome-wide association studies (GWAS) [4-8]. To identify the genetic basis of GVHD, we conducted GWAS by genotyping more than 500,000

Solvent Effects on the Structure-Activity Relationship of Phenytoin-like Anticonvulsant Drugs

The absorption spectra of nine compounds structurally related to phenytoin (5,5-diphenylhydantoin) were recorded in twelve solvents over the range of 200 to 400 nm. The effects of solvent dipolarity/polarizability and solvent/solute hydrogen bonding interactions were analyzed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The lipophilic activity of the investigated hydantoins was estimated by calculation of their log 10 P values. The calculated values of log 10 P were correlated with the ratio of the contributions of specific and non-specific solute/solvent interactions. The correlation equations were combined with the corresponding ED50 values to generate new equations that demonstrate exact relationship between solute/solvent interactions and the structure-activity parameters.