Browsing by Subject "Principal Component Analysis"
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Item Assessing Ecogeographical Variation in the Nasal Passages Utilizing 3D Semilandmarks(2021-05) Ward, Lyndee A.; Maddux, Scott D.; Menegaz, Rachel A.; Handler, EmmaPrior research has shown strong statistical relationships between geographically-patterned variation in nasal skeletal morphology and global climatic conditions. Specifically, the nasal skeletons of individuals indigenous to cold-dry environments tend to be longer, taller, and especially narrower, than those from hot-humid environments. As the nasal passages heat and humidify inspired air for entry into the lungs, this morphological patterning is believed to reflect the specific air-conditioning demands of different climates. However, while it is widely assumed the morphology of the nasal skeleton accurately reflects that of the functional (soft-tissue) nasal passages, the existence of ecogeographic variation in the three-dimensional (3D) nasal soft tissues has yet to be empirically demonstrated. This study investigates 3D shape variation in decongested soft-tissue nasal passages of individuals ancestrally derived from cold-dry (CD) and hot-humid (HH) environments (n=20). Using 3D Slicer and Avizo, a total of 260 semilandmarks were collected from the decongested nasal passages of Each individual. General Procrustes Analysis (GPA) was then used to align the semilandmark configurations of all 20 individuals and a Principal Component Analysis (PCA) was subsequently performed using the Geomorph package in R. Our results indicate PC1 (19.13%) largely contrasts CD individuals with positive PC1 scores (relatively narrower nasal passages) from HH individuals with negative PC1 scores (relatively wider nasal passages). These results generally conform to morphological expectations, suggesting a general concordance between skeletal and decongested soft-tissue nasal anatomy. This study thus provides the impetus for future research investigating the relationship between ecogeographic variation in nasal soft-tissue anatomy and air-conditioning physiology.Item Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery(PLOS, 2016-04-26) Kalescky, Robert; Zhou, Hongyu; Liu, Jin; Tao, PengIntra-protein information is transmitted over distances via allosteric processes. This ubiquitous protein process allows for protein function changes due to ligand binding events. Understanding protein allostery is essential to understanding protein functions. In this study, allostery in the second PDZ domain (PDZ2) in the human PTP1E protein is examined as model system to advance a recently developed rigid residue scan method combining with configurational entropy calculation and principal component analysis. The contributions from individual residues to whole-protein dynamics and allostery were systematically assessed via rigid body simulations of both unbound and ligand-bound states of the protein. The entropic contributions of individual residues to whole-protein dynamics were evaluated based on covariance-based correlation analysis of all simulations. The changes of overall protein entropy when individual residues being held rigid support that the rigidity/flexibility equilibrium in protein structure is governed by the La Chatelier's principle of chemical equilibrium. Key residues of PDZ2 allostery were identified with good agreement with NMR studies of the same protein bound to the same peptide. On the other hand, the change of entropic contribution from each residue upon perturbation revealed intrinsic differences among all the residues. The quasi-harmonic and principal component analyses of simulations without rigid residue perturbation showed a coherent allosteric mode from unbound and bound states, respectively. The projection of simulations with rigid residue perturbation onto coherent allosteric modes demonstrated the intrinsic shifting of ensemble distributions supporting the population-shift theory of protein allostery. Overall, the study presented here provides a robust and systematic approach to estimate the contribution of individual residue internal motion to overall protein dynamics and allostery.Item Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study(BioMed Central Ltd., 2017-12-19) Robinson, Michelle D.; Mishra, Ina; Deodhar, Sneha; Patel, Vipulkumar; Gordon, Katrina V.; Vintimilla, Raul; Brown, Kim; Johnson, Leigh A.; O'Bryant, Sid E.; Cistola, David P.BACKGROUND: Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic beta-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement. METHODS: Water T2, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. RESULTS: Plasma and serum water T2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma. CONCLUSIONS: Water T2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual's metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.