Gaussian Process Modeling of Protein Turnover.
*Brain Chemistry; *dynamic proteome; *Gaussian process; *mass spectrometry; *Ornstein-Uhlenbeck process; *protein degradation rate constant; *protein turnover rate constant; *stable isotope labeling; *stochastic differential equation for protein turnover rate constant; Animals; Chromatography; Data Interpretation; Isotope Labeling; Kinetics; Liquid; Liver/*chemistry; Mass Spectrometry; Mice; Normal Distribution; Proteins/*metabolism; Proteome/*metabolism; Proteomics/methods; Statistical; Stochastic Processes
We describe a stochastic model to compute in vivo protein turnover rate constants from stable-isotope labeling and high-throughput liquid chromatography-mass spectrometry experiments. We show that the often-used one- and two-compartment nonstochastic models allow explicit solutions from the corresponding stochastic differential equations. The resulting stochastic process is a Gaussian processes with Ornstein-Uhlenbeck covariance matrix. We applied the stochastic model to a large-scale data set from (15)N labeling and compared its performance metrics with those of the nonstochastic curve fitting. The comparison showed that for more than 99% of proteins, the stochastic model produced better fits to the experimental data (based on residual sum of squares). The model was used for extracting protein-decay rate constants from mouse brain (slow turnover) and liver (fast turnover) samples. We found that the most affected (compared to two-exponent curve fitting) results were those for liver proteins. The ratio of the median of degradation rate constants of liver proteins to those of brain proteins increased 4-fold in stochastic modeling compared to the two-exponent fitting. Stochastic modeling predicted stronger differences of protein turnover processes between mouse liver and brain than previously estimated. The model is independent of the labeling isotope. To show this, we also applied the model to protein turnover studied in induced heart failure in rats, in which metabolic labeling was achieved by administering heavy water. No changes in the model were necessary for adapting to heavy-water labeling. The approach has been implemented in a freely available R code.
Rahman Mahbubur; Previs Stephen F; Kasumov Takhar; Sadygov Rovshan G
Journal of proteome research
2016
2016-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1021/acs.jproteome.5b00990" target="_blank" rel="noreferrer noopener">10.1021/acs.jproteome.5b00990</a>
Intracellular recording reveals temporal integration in inferior colliculus neurons of awake bats.
Acoustic Stimulation; Animals; Chiroptera/*physiology; Data Interpretation; Electrophysiology; Excitatory Postsynaptic Potentials/physiology; Inferior Colliculi/cytology/*physiology; Inhibitory Postsynaptic Potentials/physiology; Microelectrodes; Neurons/*physiology; Pitch Perception; Statistical
The central nucleus of the inferior colliculus (IC) is a major integrative center in the central auditory system. It receives information from both the ascending and descending auditory pathways. To determine how single IC neurons integrate information over a wide range of sound frequencies and sound levels, we examined their intracellular responses to frequency-modulated (FM) sounds in awake little brown bats (Myotis lucifugus). Postsynaptic potentials were recorded in response to downward FM sweeps of the range typical for little brown bats (80-20 kHz) and to three FM subcomponents (80-60, 60-40, and 40-20 kHz). The majority of recorded neurons responded to the 80- to 20-kHz downward FM sweep with a complex response. In this response an initial hyperpolarization was followed by depolarization with or without spike followed by hyperpolarization. Intracellular recordings in response to three FM subcomponents revealed that these neurons receive excitatory and inhibitory inputs from a wide range of sound frequencies. One third of IC neurons performed nearly linear temporal summation across a wide range of sound frequencies, whereas two thirds of IC neurons exhibited nonlinear summation with different degrees of nonlinearity. Some IC neurons showed different latencies of postsynaptic potentials in response to different FM subcomponents. Often responses to the later FM subcomponent occurred before responses to the earlier ones. This phenomenon may be responsible for response selectivity of IC neurons to FM sweeps.
Voytenko S V; Galazyuk A V
Journal of neurophysiology
2007
2007-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.00976.2006" target="_blank" rel="noreferrer noopener">10.1152/jn.00976.2006</a>
Weighted Lin-Wang tests for crossing hazards.
*Survival Analysis; Algorithms; Animal; Animals; Computer Simulation; Data Interpretation; Disease Models; Humans; Kaplan-Meier Estimate; Leukemia/drug therapy; Mice; Models; Reproducibility of Results; Statistical
Lin and Wang have introduced a quadratic version of the logrank test, appropriate for situations in which the underlying survival distributions may cross. In this note, we generalize the Lin-Wang procedure to incorporate weights and investigate the performance of Lin and Wang's test and weighted versions in various scenarios. We find that weighting does increase statistical power in certain situations; however, none of the procedures was dominant under every scenario.
Koziol James A; Jia Zhenyu
Computational and mathematical methods in medicine
2014
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1155/2014/643457" target="_blank" rel="noreferrer noopener">10.1155/2014/643457</a>
A note regarding problems with interaction and varying block sizes in a comparison of endotracheal tubes.
*Randomized Controlled Trials as Topic; *Research Design; Algorithms; Anesthesiology/*methods; Data Interpretation; Humans; Intratracheal/*instrumentation; Intubation; Models; Sample Size; Statistical; Treatment Outcome
A randomized clinical experiment to compare two types of endotracheal tubes utilized a block design where each of the six participating anesthesiologists performed tube insertions for an equal number of patients for each type of tube. Five anesthesiologists intubated at least three patients with each tube type, but one anesthesiologist intubated only one patient per tube type. Overall, one type of tube outperformed the other on all three effectiveness measures. However, analysis of the data using an interaction model gave conflicting and misleading results, making the tube with the better performance appear to perform worse. This surprising result was caused by the undue influence of the data for the anesthesiologist who intubated only two patients. We therefore urge caution in interpreting results from interaction models with designs containing small blocks.
Einsporn Richard L; Jia Zhenyu
Computational and mathematical methods in medicine
2014
1905-7
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1155/2014/956917" target="_blank" rel="noreferrer noopener">10.1155/2014/956917</a>
Reading qualitative research from a methodological point of view.
Humans; Ohio; Patient Satisfaction; Evaluation Studies as Topic; Research Design/standards; Program Evaluation/*methods; Aftercare; *Crime Victims; Community Health Services/organization & administration/standards; Health Services Research/*methods/standards; Process Assessment (Health Care); Voluntary Health Agencies/*organization & administration/standards; Statistical; Data Interpretation
Cuevas N M; Dinero T E; Feit M D
Journal of health & social policy
1996
1996
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1300/J045v08n01_07" target="_blank" rel="noreferrer noopener">10.1300/J045v08n01_07</a>
Test for linear trend in 2 x K ordered tables with open-ended categories.
Humans; *Forecasting; Biometry/methods; Epidemiologic Methods; Physical Fitness; Television/trends; Statistical; *Models; Data Interpretation
A method of evaluating trend (positive or negative) in 2 x K ordered tables is suggested for cases in which the scores for the first (K-1) categories are known a priori but the score for the last category is not known. Such a category is termed as open-ended category in this paper. Ordered tables with an open-ended category are often encountered while evaluating the Cochran-Armitage-Mantel (CAM) trend. In the present paper, the distribution of the test statistic is presented and simulations are carried out to check the asymptotics. The method is then exemplified by an existing data set.
Gautam S
Biometrics
1997
1997-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.2307/2533575" target="_blank" rel="noreferrer noopener">10.2307/2533575</a>