Bayesian analysis of amino acid substitution models

Models of amino acid substitution present challenges beyond those often faced with the analysis of DNA sequences. The alignments of amino acid sequences are often small, whereas the number of parameters to be estimated is potentially large when compared with the number of free parameters for nucleotide substitution models. Most approaches to the analysis of amino acid alignments have focused on the use of fixed amino acid models in which all of the potentially free parameters are fixed to values estimated from a large number of sequences. Often, these fixed amino acid models are specific to a gene or taxonomic group (e.g. the Mtmam model, which has parameters that are specific to mammalian mitochondrial gene sequences). Although the fixed amino acid models succeed in reducing the number of free parameters to be estimated--indeed, they reduce the number of free parameters from approximately 200 to 0--it is possible that none of the currently available fixed amino acid models is appropriate for a specific alignment. Here, we present four approaches to the analysis of amino acid sequences. First, we explore the use of a general time reversible model of amino acid substitution using a Dirichlet prior probability distribution on the 190 exchangeability parameters. Second, we then explore the behaviour of prior probability distributions that are'centred' on the rates specified by the fixed amino acid model. Third, we consider a mixture of fixed amino acid models. Finally, we consider constraints on the exchangeability parameters as partitions,similar to how nucleotide substitution models are specified, and place a Dirichlet process prior model on all the possible partitioning schemes.     

呼吸科与重症监护室院内获得性肺炎预后因素分析

目的通过对浙江大学医学院附属第一医院呼吸科和监护室（ICU）院内获得性肺炎（HAP）患者资料进行回顾性分析,以寻找不同科室患者HAP发生的危险因素的异同,从而针对不同人群建立特异的预防HAP的决策。方法采取回顾性研究,收集2011年6月1日至2013年9月30日浙江大学附属第一医院呼吸科和ICU出院诊断为肺炎（年龄≥18岁）的病历资料,比较两科室患者基本资料、基础疾病等方面的差别,然后对HAP患者危险因素进行分析,对筛选出来的P〈0.05的因素再进行Logistic多因素回归分析。结果逐步Logistic回归（Backward：Wald）分析提示,呼吸科危险因素为血液及实体肿瘤病史而ICU危险因素为感染性休克与近期重大手术史。结论两科室存在不同的影响预后的危险因素,ICU院内获得性肺炎的发病率、死亡率明显高于呼吸科,这与患者基础疾病有密切关系。     

Incorporating prior beliefs about selection bias into the analysis of randomized trials with missing outcomes

In randomized studies with missing outcomes, non-identifiable assumptions are required to hold for valid data analysis. As a result, statisticians have been advocating the use of sensitivity analysis to evaluate the effect of varying assumptions on study conclusions. While this approach may be useful in assessing the sensitivity of treatment comparisons to missing data assumptions, it may be dissatisfying to some researchers/decision makers because a single summary is not provided. In this paper, we present a fully Bayesian methodology that allows the investigator to draw a 'single' conclusion by formally incorporating prior beliefs about non-identifiable, yet interpretable, selection bias parameters. Our Bayesian model provides robustness to prior specification of the distributional form of the continuous outcomes.     

A hybrid model for reducing ecological bias

A major drawback of epidemiological ecological studies, in which the association between area-level summaries of risk and exposure is used to make inference about individual risk, is the difficulty in characterizing within-area variability in exposure and confounder variables. To avoid ecological bias, samples of individual exposure/confounder data within each area are required. Unfortunately, these may be difficult or expensive to obtain, particularly if large samples are required. In this paper, we propose a new approach suitable for use with small samples. We combine a Bayesian nonparametric Dirichlet process prior with an estimating functions' approach and show that this model gives a compromise between 2 previously described methods. The method is investigated using simulated data, and a practical illustration is provided through an analysis of lung cancer mortality and residential radon exposure in counties of Minnesota. We conclude that we require good quality prior information about the exposure/confounder distributions and a large between- to within-area variability ratio for an ecological study to be feasible using only small samples of individual data.     

Prediction of regulation relationship between protein interactions in signaling networks

The discovery of regulation relationship of protein interactions is crucial for the mechanism research in signaling network. Bioinformatics methods can be used to accelerate the discovery of regulation relationship between protein interactions, to distinguish the activation relations from inhibition relations. In this paper, we describe a novel method to predict the regulation relations of protein interactions in the signaling network. We detected 4,417 domain pairs that were significantly enriched in the activation or inhibition dataset. Three machine learning methods, logistic regression, support vector machines(SVMs), and naïve bayes, were explored in the classifier models. The prediction power of three different models was evaluated by 5-fold cross-validation and the independent test dataset. The area under the receiver operating characteristic curve for logistic regression, SVM, and naïve bayes models was 0.946, 0.905 and 0.809, respectively. Finally, the logistic regression classifier was applied to the human proteome-wide interaction dataset, and 2,591 interactions were predicted with their regulation relations, with 2,048 in activation and 543 in inhibition. This model based on domains can be used to identify the regulation relations between protein interactions and furthermore reconstruct signaling pathways.