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PubMedDate not supplied

Toxicokinetics/toxicodynamic correlations: goals, methods, and limitations.

Toxicokinetic (TK) studies are the basis for demonstrating dose-related drug exposure in animals and for ensuring that drug exposure is substantially greater in animals than that expected in humans at therapeutic doses. The usefulness of TK studies can be further enhanced by correlating TK parameters with relevant toxicologic end points. The so-called TK/toxicodynamic (TD) correlations can be extremely useful in bridging data from studies both within and across species and in designing early Phase I clinical trials. These correlations assume that toxicologic responses are comparable among species at comparable plasma concentrations. This assumption may apply for certain drugs but not for others. Therefore, TK/TD correlations should be developed and utilized on a case-by-case basis. Such correlations have proven to be extremely useful with anticancer drugs in formulating dose escalation strategies in cancer patients to rapidly attain the maximum tolerated and/or effective dose. However, these correlations have not been utilized effectively in other therapeutic areas. The development of TK/TD correlations, their scope, and limitations are discussed in this paper.

Animals↗

PubMed1985

Correlations between cancer mortality rates from various Italian regions.

Death certification rates from 17 non-sexual and 4 sexual cancers were used to examine patterns of correlation between various cancers within the 20 Italian regions. A large number of strongly positive correlations emerged, reflecting the geographical distribution of cancer mortality in Italy which shows substantially higher rates for several common sites in northern areas. The most notable findings were the high positive correlations between various tobacco-related cancers in both sexes (however somewhat higher in males), the positive correlations between most intestinal sites and between a well defined group of other cancers including intestines in both sexes, breast and ovary in females and prostate in males, previously described in several widely heterogeneous populations. Various alcohol-related cancers showed high positive coefficients in males but not in females. Several suggestions which emerged from previous correlation studies but which generally lacked convincing biological or epidemiological consistency were not confirmed by the present data. Conversely, a few strong correlations emerged in the present study which are not explainable in terms of available knowledge of the causes of cancer, or obvious confounding. Though probably incidental, the existence of these correlations between cancers with widely heterogeneous or largely undefined etiology is still an indirect indication that these neoplasms are largely avoidable, since it is unlikely that the same genetic determinants are strongly associated with such different malignancies.

Female↗

PubMed1999

The correlation between the severity of peripheral arterial disease and carotid occlusive disease.

Peripheral arterial disease (PAD) and carotid occlusive disease (COD) are both known to be specific manifestations of atherosclerosis. Because they both have a common cause, it is reasonable to hypothesize that they should correlate with each other to a certain extent, and previous studies have shown that there is a correlation between the prevalence of PAD and COD. The purpose of this study was to determine whether a correlation exists between the severity of PAD and the severity of COD by retrospectively looking at a group of 203 patients who underwent non-invasive testing for suspicion of PAD at the San Diego VA Hospital or UCSD Medical Center, and who also had a non-invasive duplex carotid scan. The severity of PAD was assessed by segmental blood pressure ratios (leg segment/arm ratio) in each leg taken at the toe, ankle, and below the knee, as well as the peak flow velocity of the posterior tibial artery. The severity of COD was assessed by duplex ultrasound scans of six distinct segments of the carotid artery system: the right and left common, internal, and external carotid arteries. Correlation analysis showed r=0.23 (p=0.001) when comparing a PAD aggregate standard score with the number of diseased carotid arteries (>50% stenosis), and r=0.23 (p=0.001) when comparing a PAD aggregate standard score with an average COD score. Because about 50% of the patients had undergone surgical intervention on their leg or carotid arteries, another correlation analysis restricted to patients with no surgical interventions (n = 97) was performed. The above correlations were slightly attenuated in this analysis, r=0.21 (p=0.043) and r=0.17 (p= 0.092), respectively. The results indicate that there is a modest but significant correlation between the severity of PAD and the severity of COD in a population with a high prevalence of both.

Adult↗

PubMed2004

Correlation of MR perfusion imaging and vessel tortuosity parameters in assessment of intracranial neoplasms.

Advances in noninvasive imaging techniques such as magnetic resonance perfusion imaging have been found useful in grading cerebral neoplasms and have potential for significant clinical benefit. The purpose of this study was to determine the correlation between tumor vessel tortuosity as measured from vessels extracted from magnetic resonance angiograms (MRA) and perfusion parameters of cerebral blood flow (CBF) and cerebral blood volume (CBV) in intracranial neoplasms. We hypothesized that tumor blood vessel tortuosity measures and perfusion measures would be correlated, since both are increased by tumor angiogenesis. 18 patients with 19 cerebral neoplasms were evaluated with conventional MR imaging and dynamic contrast-enhanced T2-weighted perfusion MR imaging (PWI). Both benign and malignant lesions were included, as were hyper- and hypovascular tumors. Regions of interest were plotted within the tumor area to locate foci of maximum CBV and CBF. CBV and CBF measurements were also recorded in contralateral normal appearing white matter to calculate relative CBV (rCBV) and relative CBF (rCBF). Vessel tortuosity analyses were conducted upon vessels segmented from MRA images of the same patients using two tortuosity descriptors (SOAM and ICM), which have previously been demonstrated to have efficacy in separating benign from malignant disease. Linear regression analyses were conducted to determine if correlations exist between CBV or CBF and the two tortuosity measurements. For the overall set of tumors, no significant correlations were found between flow or volume measures and the tortuosity measures. However, when the 7 glioblastoma multiforme tumors were examined as a subgroup, the following significant correlations were found: rCBV and SOAM (R2=0.799), rCBV and ICM (R2=0.214). Our results demonstrate that MR perfusion imaging data do not correlate significantly with vessel tortuosity parameters as determined from the larger vessels seen by MRA. However, for subgroups of a particular tumor type such as GBM, there may be significant correlations. It appears that perfusion and tortuosity data may provide independently useful data in the assessment of cerebral neoplasms.

Brain Neoplasms↗

PubMed2005

Endoscopic and histologic evidence of persistent mucosal healing and correlation with clinical improvement following sustained infliximab treatment for Crohn's disease.

OBJECTIVES: The long-term effect of infliximab on endoscopic and histologic disease activity and expression of inflammatory markers was assessed in Crohn's disease patients who received infliximab as episodic or scheduled maintenance therapy therapy over 54 weeks (ACCENT 1). METHODS: All patients received Infliximab 5 mg/kg at week 0 and at week 2 were then randomized as responders or nonresponders to placebo or infliximab (5 or 10mg/kg). Patients received placebo or infliximab 5 mg/kg at weeks 2 and 6 followed by placebo or infliximab (5 or 10mg/kg) every 8 weeks or episodically on loss of response. Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), Inflammatory Bowel Disease Questionnaire (IBDQ), and colonic and ileal Global Histologic Disease Activity (CGHAS and IGHAS) scores were determined at weeks 0, 10, and 54. Tumor necrosis factor-alpha (TNF-alpha), gelatinase B, Infliximab, tenascin, clusters of differentiation marker 68 (CD68), and intercellular adhesion molecule-1 (ICAM-1) were detected in mucosal biopsies by immunohistochemistry. RESULTS: At baseline, CDEIS significantly correlated with CGHAS only. Further at baseline, both CDEIS and the worst CGHAS or IGHAS, were significantly correlated with CD68, ICAM-1, and gelatinase B expression. At week 10, improvement in CGHAS only, correlated significantly with better CDAI, CDEIS, and IBDQ scores. Improvements in CDEIS and GHAS at week 10 correlated with reductions in gelatinase B and CD68, whereas only GHAS improvement correlated with decreased TNF-alpha expression. At week 54, decreased gelatinase B expression continued to correlate with improved CDEIS and GHAS while decreased CD68 and TNF-alpha expression correlated with GHAS and CDEIS improvement, respectively. CONCLUSIONS: Endoscopic and histologic evidence of mucosal healing was associated with a sustained reduction in the expression of inflammatory markers. Infliximab-induced improvement in the clinical signs and symptoms of Crohn's disease was associated with endoscopic and histologic evidence of sustained mucosal healing.

Adult↗

PubMed2006

Correlation of improved erectile function and rate of successful intercourse with improved emotional well-being assessed with the Self-Esteem And Relationship questionnaire in men treated with sildenafil for erectile dysfunction and stratified by age.

BACKGROUND: The quality of life consequences of erectile dysfunction (ED) include depression, anxiety, and loss of self-esteem. The Self-Esteem And Relationship (SEAR) questionnaire is a validated, patient-administered, psychometric instrument specific to ED. OBJECTIVE: To determine correlations between erectile function (EF), intercourse success, and emotional well-being measured with the SEAR questionnaire in men treated with sildenafil citrate for ED and stratified by age (< 50 years, 50-65 years, and > 65 years). RESEARCH DESIGN AND METHODS: This was an open-label, flexible-dose trial of sildenafil (25, 50 and 100 mg) administered for 10 weeks to 382 men with ED (mean +/- SD age, 55 +/- 13 years; mean ED duration, 4 years), which was conducted at 62 centers in the United States. MAIN OUTCOME MEASURES: Analysis (by intent-to-treat, n = 368) of the change from baseline to the week-10 endpoint in the SEAR questionnaire Self-Esteem subscale, the intercourse success rate (percent of occasions at which an erection that lasted long enough for successful intercourse was achieved), and their correlation. RESULTS: For the overall population, there was mean +/- SD improvement (p < 0.0001, paired t-tests) in the Self-Esteem subscale (56 +/- 25 to 79 +/- 22) and intercourse success rate (21 +/- 30% to 70 +/- 36%), which showed positive correlation (p < 0.0001). Secondary outcomes (i.e., EF domain of the International Index of Erectile Function; event log frequency of erection hard enough for sexual intercourse and of ejaculation/orgasm) also improved (p < 0.0001) and correlated positively with the SEAR Self-Esteem subscale and Sexual Relationship domain (p < 0.05 for all correlations). All 10 correlations were positive (p < 0.05) in men aged 50 to 65 years, eight were positive in men aged > 65 years, and six were positive in men aged < 50 years. The most common treatment-related adverse events were mild-to-moderate headache (12% of patients), vasodilatation (7%), and rhinitis (4%). CONCLUSIONS: Men treated with sildenafil for ED demonstrated improved erectile function and an increased intercourse success rate, which correlated positively with improvement in SEAR measures of self-esteem and sexual relationship.

Adult↗

PubMed2005

Modelling the correlation between the activities of adjacent genes in Drosophila.

BACKGROUND: Correlation between the expression levels of genes which are located close to each other on the genome has been found in various organisms, including yeast, drosophila and humans. Since such a correlation could be explained by several biochemical, evolutionary, genetic and technological factors, there is a need for statistical models that correspond to specific biological models for the correlation structure. RESULTS: We modelled the pairwise correlation between the expressions of the genes in a Drosophila microarray experiment as a normal mixture under Fisher's z-transform, and fitted the model to the correlations of expressions of adjacent as well as non-adjacent genes. We also analyzed simulated data for comparison. The model provided a good fit to the data. Further, correlation between the activities of two genes could, in most cases, be attributed to either of two factors: the two genes both being active in the same age group (adult or embryo), or the two genes being in proximity of each other on the chromosome. The interaction between these two factors was weak. CONCLUSIONS: Correlation between the activities of adjacent genes is higher than between non-adjacent genes. In the data we analyzed, this appeared, for the most part, to be a constant effect that applied to all pairs of adjacent genes.

Algorithms↗

PubMed2005

Correlation and prediction of gene expression level from amino acid and dipeptide composition of its protein.

BACKGROUND: A large number of papers have been published on analysis of microarray data with particular emphasis on normalization of data, detection of differentially expressed genes, clustering of genes and regulatory network. On other hand there are only few studies on relation between expression level and composition of nucleotide/protein sequence, using expression data. There is a need to understand why particular genes/proteins express more in particular conditions. In this study, we analyze 3468 genes of Saccharomyces cerevisiae obtained from Holstege et al., (1998) to understand the relationship between expression level and amino acid composition. RESULTS: We compute the correlation between expression of a gene and amino acid composition of its protein. It was observed that some residues (like Ala, Gly, Arg and Val) have significant positive correlation (r > 0.20) and some other residues (Like Asp, Leu, Asn and Ser) have negative correlation (r < -0.15) with the expression of genes. A significant negative correlation (r = -0.18) was also found between length and gene expression. These observations indicate the relationship between percent composition and gene expression level. Thus, attempts have been made to develop a Support Vector Machine (SVM) based method for predicting the expression level of genes from its protein sequence. In this method the SVM is trained with proteins whose gene expression data is known in a given condition. Then trained SVM is used to predict the gene expression of other proteins of the same organism in the same condition. A correlation coefficient r = 0.70 was obtained between predicted and experimentally determined expression of genes, which improves from r = 0.70 to 0.72 when dipeptide composition was used instead of residue composition. The method was evaluated using 5-fold cross validation test. We also demonstrate that amino acid composition information along with gene expression data can be used for improving the function classification of proteins. CONCLUSION: There is a correlation between gene expression and amino acid composition that can be used to predict the expression level of genes up to a certain extent. A web server based on the above strategy has been developed for calculating the correlation between amino acid composition and gene expression and prediction of expression level http://kiwi.postech.ac.kr/raghava/lgepred/. This server will allow users to study the evolution from expression data.

Algorithms↗

PubMed2003

Use of a new fluorescence immunoassay to detect anti-dsDNA antibodies is more correlated with disease activity and complement than the ELISA method in SLE patients.

To determine whether the serum levels of anti-double strand DNA (anti-dsDNA) autoantibodies detected using a newly developed fluorescence immunoassay (FIA) in patients with systemic lupus erythematosus (SLE) correlated more with clinical parameters, such as SLE disease activity index (SLEDAI), complement and the occurrence of nephritis when compared with traditional enzyme-linked immunosorbent assay (ELISA), we prospectively collected 124 serum samples from 31 patients who had juvenile-onset SLE and were regularly monitored every 2 months at our outpatient clinic. At every visit, clinical manifestations and laboratory parameters were assessed and the SLEDAI was determined. Correlation analyses between the two different measurements of anti-dsDNA antibodies and SLEDAI, serum complement levels and the occurrence of nephritis were performed. The results showed that anti-dsDNA autoantibodies detected using both ELISA and FIA significantly correlated with SLEDAI, and significantly and inversely correlated with the serum levels of C3 and C4. FIA had significantly higher correlation with SLEDAI and C4 than did ELISA. The mean values of anti-dsDNA antibodies detected using FIA in patients with nephritis were significantly higher than in those without nephritis. In contrast, the values of anti-dsDNA antibodies detected using ELISA did not show significant differences between these two groups. We conclude that FIA had better correlation with SLEDAI, C4 and the occurrence of nephritis, and comparable correlations with C3 that were similar to the results found using ELISA. Thus, it is worthwhile developing the FIA method for clinical evaluation of disease activity in SLE patients.

Adolescent↗

PubMed1992

Normal and elevated 3 alpha-androstanediol glucuronide concentrations in women with various causes of hirsutism and its correlation with degree of hirsutism and androgen levels.

We investigated peripheral androgen metabolic activity in 54 hirsute females (HF) by evaluating the serum 3 alpha-androstanediol glucuronide (3AG) concentration, hirsutism score (HS), and etiology of hirsutism. Based on basal and ACTH-stimulated steroid profiles (1 h post-Cortrosyn, 0.25 mg, i.v. bolus), the causes of hirsutism were determined to be increased adrenal androgen production (greater than 2 SD above normal mean), increased ovarian testosterone (T) production (greater than 2 SD above normal mean basal T of ovarian source only), or idiopathic cause (normal steroid profile). Serum 3AG levels in each group of HF were significantly higher (P less than 0.01-0.001) than those in normal females [normal: 2.9 +/- 0.94 nmol/L (n = 28); HF: increased adrenal androgen production of undefined cause, 7.7 +/- 7.5 nmol/L (n = 14); 21-hydroxylase deficiency, 7.6 +/- 7.4 nmol/L (n = 5); increased ovarian T production 5.5 +/- 3.5 nmol/L (n = 18); idiopathic cause, 5.8 +/- 4.8 nmol/L (n = 17)]. However, normal 3AG levels (less than 5.2 nmol/L) were present in 50-67% of HF in each group. Collectively, 3AG levels in HF correlated significantly (P less than 0.01) with dehydroepiandrosterone (DHEA; r = 0.41) and DHEA sulfate (DS; r = 0.44), while the correlation with androstenedione (r = 0.15) or T (r = 0.19) was not significant. Serum 3AG and adrenal androgen levels decreased in all subjects after dexamethasone treatment (0.5-1 mg at hour of sleep; 2 mg/day for 3-5 days). The correlation between 3AG and HS was significant (r = 0.6-0.74; P less than 0.01-0.001) only in HF with increased adrenal androgen secretion and idiopathic cause, and was not significant (r = 0.42) in HF with increased ovarian T secretion. There was no significant correlation between androgen levels and HS. We conclude that the serum 3AG level was not consistently elevated in HF and did not differ significantly between the various causes. Significant correlations between 3AG and DHEA/DS levels, and the simultaneous decrease in 3AG and adrenal androgens after dexamethasone administration in HF suggest that adrenal androgens contribute significantly to 3AG production. The significant correlation between 3AG and HS in HF with increased adrenal androgen secretion and idiopathic cause indirectly suggests an adrenal androgen contribution to both 3AG production and hirsutism in these HF. The insignificant correlation between 3AG and HS in HF with increased ovarian T secretion may result from a confounding effect of ovarian T on hirsutism.

Adolescent↗

PubMed1999

Clinical and quantitative pathologic correlates of dementia with Lewy bodies.

OBJECTIVES: To examine the distribution of cortical Lewy bodies (LB) and their contribution to the clinical syndrome in dementia with LB (DLB) and to address their relationship to the pathologic markers of AD and PD. METHODS: We studied 25 cases meeting neuropathologic criteria for DLB: 13 cases without AD (Braak stage I or II) and 12 cases with concomitant AD changes (Braak stages III to V). Age at onset, disease duration, and clinical symptoms were reviewed for each case. We quantified the regional distribution of LB in substantia nigra, paralimbic areas (cingulate gyrus, insula, entorhinal cortex, and hippocampus), and neocortex (frontal and occipital association areas) using anti-alpha-synuclein immunostaining. We compared the LB pathology between groups of patients with different symptoms at onset or with specific clinical phenotypes. RESULTS: There were no significant differences in clinical symptoms or LB density between cases with or without concomitant AD. LB density showed a consistent gradient as follows: substantia nigra > entorhinal cortex > cingulate gyrus > insula > frontal cortex > hippocampus > occipital cortex. LB density in substantia nigra and neocortex was not significantly different in cases that started with parkinsonism compared with those that started with dementia. There were no significant differences in LB density in any region among patients with or without cognitive fluctuations, visual hallucinations, delusions, recurrent falls, or parkinsonism. Duration of the disease correlated with a global LB burden for each case (p = 0.02) but did not correlate with LB density in any individual area. Paralimbic and neocortical LB density were highly correlated with each other (p<0.0001), but neither of these correlated well with the number of LB in substantia nigra. LB density did not correlate with Braak stage or frequency of neuritic plaques. CONCLUSIONS: There is a consistent pattern of vulnerability to LB formation across subcortical, paralimbic, and neocortical structures that is similar for DLB cases with or without concomitant AD. Paralimbic and neocortical LB do not correlate with LB in substantia nigra, suggesting that DLB should not be considered just a severe form of PD. LB density correlates weakly with clinical symptoms and disease duration.

Age of Onset↗

PubMed2003

Language functional magnetic resonance imaging in preoperative assessment of language areas: correlation with direct cortical stimulation.

OBJECTIVE: The aim of this study was to analyze the usefulness of preoperative language functional magnetic resonance imaging (fMRI), by correlating fMRI data with intraoperative cortical stimulation results for patients with brain tumors. METHODS: Naming and verb generation tasks were used, separately or in combination, for 14 right-handed patients with tumors in the left hemisphere. fMRI data obtained were analyzed with SPM software, with two standard analysis thresholds (P < 0.005 and then P < 0.05). The fMRI data were then registered in a frameless stereotactic neuronavigational device and correlated with direct brain mapping results. We used a statistical model with the fMRI information as a predictor, spatially correlating each intraoperatively mapped cortical site with fMRI data integrated in the neuronavigational system (site-by-site correlation). Eight patients were also studied with language fMRI postoperatively, with the same acquisition protocol. RESULTS: We observed high variability in signal extents and locations among patients with both tasks. The activated areas were located mainly in the left hemisphere in the middle and inferior frontal gyri (F2 and F3), the superior and middle temporal gyri (T1 and T2), and the supramarginal and angular gyri. A total of 426 cortical sites were tested for each task among the 14 patients. In frontal and temporoparietal areas, poor sensitivity of the fMRI technique was observed for the naming and verb generation tasks (22 and 36%, respectively) with P < 0.005 as the analysis threshold. Although not perfect, the specificity of the fMRI technique was good in all conditions (97% for the naming task and 98% for the verb generation task). Better correlation (sensitivity, 59%; specificity, 97%) was achieved by combining the two fMRI tasks. Variation of the analysis threshold to P < 0.05 increased the sensitivity to 66% while decreasing the specificity to 91%. Postoperative fMRI data (for the cortical brain areas studied intraoperatively) were in accordance with brain mapping results for six of eight patients. Complete agreement between pre- and postoperative fMRI studies and direct brain mapping results was observed for only three of eight patients. CONCLUSION: With the paradigms and analysis thresholds used in this study, language fMRI data obtained with naming or verb generation tasks, before and after surgery, were imperfectly correlated with intraoperative brain mapping results. A better correlation could be obtained by combining the fMRI tasks. The overall results of this study demonstrated that language fMRI could not be used to make critical surgical decisions in the absence of direct brain mapping. Other acquisition protocols are required for evaluation of the potential role of language fMRI in the accurate detection of essential cortical language areas.

Adolescent↗

PubMed2004

On the correlation of a naturally and an artificially dichotomized variable.

A method is suggested for estimating the correlation of a naturally (X) and an artificially (Y) dichotomized variable. It is assumed that a normal random variable (L) underlies the artificially dichotomized variable. The proposed correlation coefficient recovers the product moment correlation coefficient between X and L from a fourfold table of X and Y. The suggested correlation coefficient nu is contrasted with the phi correlation and the biserial eta. The biserial eta was proposed by Karl Pearson and is conceptually related to the new correlation coefficient. However, in addition, Pearson's biserial eta invokes the assumption that the marginal distribution of L is normal, which contradicts its basic assumptions and thus does not recover the true correlation of L and X. Finally, an approximation is provided to simplify the calculation of nu and its standard error.

Humans↗

PubMed2001

Meaning-seeking in the illusory correlation paradigm: the active role of participants in the categorization process.

The present research examines the role of categorical perception (McGarty, Haslam, Turner, & Oakes, 1993) in the illusory correlation paradigm. This approach assumes that the search for meaningful differences between two stimulus groups can lead to the illusory correlation effect. This explanation is investigated in Study 1 by presenting participants with constrained stimulus information and examining whether accentuating evaluative differences between stimuli could provide a basis for illusory correlation. Results of this study (N = 64) revealed illusory correlation effects that were related to evaluative reinterpretations of the stimuli. Study 2 (N = 19) focused on the causal relation between illusory correlation and accentuation effects, using the thinking-aloud technique. Detailed analyses of each participants' behaviour indicated that illusory correlation can arise from actively seeking intergroup differences and that reinterpretations of stimuli and the perception of illusory correlation were mutually reinforcing. Implications of these results for stereotyping processes are discussed.

Adult↗

PubMed2002

Do health promotion messages target cognitive and behavioural correlates of condom use? A content analysis of safer sex promotion leaflets in two countries.

OBJECTIVE: To categorize and quantify the content of publicly available safer sex promotion leaflets in the UK and Germany and to assess the extent to which this content corresponds to the cognitive and behavioural correlates of condom use identified by theory-based research. METHODS: A content analysis using a 45 category coding manual was undertaken. The manual included 20 'correlate-representative' categories identifying text promoting the strongest cognitive and behavioural correlates of condom use. RESULTS: Overall inter-coder reliability was high. Few content differences were observed between the German and UK samples. Leaflets from both countries highlighted information on how people become infected with HIV and advice to contact health care professionals. Few mentioned delaying or abstaining from sexual intercourse. Only 25% of leaflets included text that referred to more than 10 of the 20 correlate-representative categories. Moreover, using one standard deviation above the mean as an indication of frequent inclusion, two-thirds of leafets failed to target frequently more than two of the 20 correlate-representative categories. CONCLUSIONS: Some safer sex promotion leaflets frequently promote the strongest cognitive and behavioural correlates of condom use. In general, however, the recommendations of researchers investigating psychological correlates of condom use have not shaped the content of safer sex promotion leaflets.

Journal Article↗

PubMed2003

New approach to generalized two-dimensional correlation spectroscopy. III: Eigenvalue manipulation transformation (EMT) for spectral selectivity enhancement.

This paper demonstrates the potential of eigenvalue manipulating transformation (EMT) of a data matrix for spectral selectivity enhancement, especially useful in 2D correlation analysis. The EMT operation aims at the accentuation of select features of the information content of the original data matrix. For example, by uniformly lowering the power of a set of eigenvalues associated with the original data, the smaller eigenvalues become more prominent and the contributions of secondary loadings become amplified. As a direct consequence of the minor factor accentuation by such EMT operations, 2D correlation spectra gain much stronger discriminating power. The selectivity enhancement effect of such manipulation of eigenvalues is much more noticeable on the synchronous 2D correlation spectrum. This improvement for the spectral selectivity of synchronous 2D correlation spectra is potentially very important, as we usually put more emphasis on the interpretation of asynchronous 2D spectra in 2D correlation analysis due to overlaps of synchronous peaks. Such EMT operations tend to exaggerate the information content of minor PCs and reduce that of major PCs. Thus, much more subtle difference of spectral behavior for each component is now highlighted. Surprisingly, asynchronous 2D correlation spectra are found to be much less sensitive to such EMT operations. The result indicates that the distinction of different band responses has already been accomplished effectively by the original asynchronous 2D correlation analysis.

Algorithms↗

PubMed2006

Combined expression trait correlations and expression quantitative trait locus mapping.

Coordinated regulation of gene expression levels across a series of experimental conditions provides valuable information about the functions of correlated transcripts. The consideration of gene expression correlation over a time or tissue dimension has proved valuable in predicting gene function. Here, we consider correlations over a genetic dimension. In addition to identifying coregulated genes, the genetic dimension also supplies us with information about the genomic locations of putative regulatory loci. We calculated correlations among approximately 45,000 expression traits derived from 60 individuals in an F2 sample segregating for obesity and diabetes. By combining the correlation results with linkage mapping information, we were able to identify regulatory networks, make functional predictions for uncharacterized genes, and characterize novel members of known pathways. We found evidence of coordinate regulation of 174 G protein-coupled receptor protein signaling pathway expression traits. Of the 174 traits, 50 had their major LOD peak within 10 cM of a locus on Chromosome 2, and 81 others had a secondary peak in this region. We also characterized a Riken cDNA clone that showed strong correlation with stearoyl-CoA desaturase 1 expression. Experimental validation confirmed that this clone is involved in the regulation of lipid metabolism. We conclude that trait correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if we studied only mRNA traits with statistically significant linkages in this small cross. The combined analysis is more sensitive compared with linkage mapping alone.

Animals↗

PubMed2005

Resolving the genetic and environmental sources of the correlation between height and intelligence: a study of nearly 2600 Norwegian male twin pairs.

The main aim of this paper was to resolve the correlation between intelligence test scores and standing height into genetic and environmental components. Data on 1181 identical and 1412 fraternal twin pairs (all males) were retrieved by matching files from the Norwegian Army with twin registries. The data were analyzed by means of a structural equation model comprising latent genetic, shared environmental and nonshared environmental factors and correlations between them. A major part of the height--intelligence correlation was due to correlated shared environments (59% of the phenotypic height--intelligence correlation), but statistically significant effects of correlated genes and nonshared environments were also found (respectively 35% and 6% of the phenotypic correlation).

Adolescent↗