Data analysis methods in optometry Part 7: multiple linear regression

Multiple regression analysis is a complex statistical method with many potential uses. It has also become one of the most abused of all statistical procedures since anyone with a data base and suitable software can carry it out. An investigator should always have a clear hypothesis in mind before carrying out such a procedure and knowledge of the limitations of each aspect of the analysis. In addition, multiple regression is probably best used in an exploratory context, identifying variables that might profitably be examined by more detailed studies. Where there are many variables potentially influencing Y, they are likely to be intercorrelated and to account for relatively small amounts of the variance. Any analysis in which R squared is less than 50% should be suspect as probably not indicating the presence of significant variables. A further problem relates to sample size. It is often stated that the number of subjects or patients must be at least 5-10 times the number of variables included in the study.5 This advice should be taken only as a rough guide but it does indicate that the variables included should be selected with great care as inclusion of an obviously unimportant variable may have a significant impact on the sample size required.

Data methods in optometry. Part 10: non-linear regression analysis

1. The techniques associated with regression, whether linear or non-linear, are some of the most useful statistical procedures that can be applied in clinical studies in optometry. 2. In some cases, there may be no scientific model of the relationship between X and Y that can be specified in advance and the objective may be to provide a ‘curve of best fit’ for predictive purposes. In such cases, the fitting of a general polynomial type curve may be the best approach. 3. An investigator may have a specific model in mind that relates Y to X and the data may provide a test of this hypothesis. Some of these curves can be reduced to a linear regression by transformation, e.g., the exponential and negative exponential decay curves. 4. In some circumstances, e.g., the asymptotic curve or logistic growth law, a more complex process of curve fitting involving non-linear estimation will be required.

Bayesian error bars for regression

Regression problems are concerned with predicting the values of one or more continuous quantities, given the values of a number of input variables. For virtually every application of regression, however, it is also important to have an indication of the uncertainty in the predictions. Such uncertainties are expressed in terms of the error bars, which specify the standard deviation of the distribution of predictions about the mean. Accurate estimate of error bars is of practical importance especially when safety and reliability is an issue. The Bayesian view of regression leads naturally to two contributions to the error bars. The first arises from the intrinsic noise on the target data, while the second comes from the uncertainty in the values of the model parameters which manifests itself in the finite width of the posterior distribution over the space of these parameters. The Hessian matrix which involves the second derivatives of the error function with respect to the weights is needed for implementing the Bayesian formalism in general and estimating the error bars in particular. A study of different methods for evaluating this matrix is given with special emphasis on the outer product approximation method. The contribution of the uncertainty in model parameters to the error bars is a finite data size effect, which becomes negligible as the number of data points in the training set increases. A study of this contribution is given in relation to the distribution of data in input space. It is shown that the addition of data points to the training set can only reduce the local magnitude of the error bars or leave it unchanged. Using the asymptotic limit of an infinite data set, it is shown that the error bars have an approximate relation to the density of data in input space.

Statnote 25: Stepwise multiple regression

An investigator may also wish to select a small subset of the X variables which give the best prediction of the Y variable. In this case, the question is how many variables should the regression equation include? One method would be to calculate the regression of Y on every subset of the X variables and choose the subset that gives the smallest mean square deviation from the regression. Most investigators, however, prefer to use a ‘stepwise multiple regression’ procedure. There are two forms of this analysis called the ‘step-up’ (or ‘forward’) method and the ‘step-down’ (or ‘backward’) method. This Statnote illustrates the use of stepwise multiple regression with reference to the scenario introduced in Statnote 24, viz., the influence of climatic variables on the growth of the crustose lichen Rhizocarpon geographicum (L.)DC.

Mathematical modelling of patient risks in a hospital environment, using multiple regression analysis

The aim of this research work was primarily to examine the relevance of patient parameters, ward structures, procedures and practices, in respect of the potential hazards of wound cross-infection and nasal colonisation with multiple resistant strains of Staphylococcus aureus, which it is thought might provide a useful indication of a patient's general susceptibility to wound infection. Information from a large cross-sectional survey involving 12,000 patients from some 41 hospitals and 375 wards was collected over a five-year period from 1967-72, and its validity checked before any subsequent analysis was carried out. Many environmental factors and procedures which had previously been thought (but never conclusively proved) to have an influence on wound infection or nasal colonisation rates, were assessed, and subsequently dismissed as not being significant, provided that the standard of the current range of practices and procedures is maintained and not allowed to deteriorate. Retrospective analysis revealed that the probability of wound infection was influenced by the patient's age, duration of pre-operative hospitalisation, sex, type of wound, presence and type of drain, number of patients in ward, and other special risk factors, whilst nasal colonisation was found to be influenced by the patient's age, total duration of hospitalisation, sex, antibiotics, proportion of occupied beds in the ward, average distance between bed centres and special risk factors. A multi-variate regression analysis technique was used to develop statistical models, consisting of variable patient and environmental factors which were found to have a significant influence on the risks pertaining to wound infection and nasal colonisation. A relationship between wound infection and nasal colonisation was then established and this led to the development of a more advanced model for predicting wound infections, taking advantage of the additional knowledge of the patient's state of nasal colonisation prior to operation.

The appraisal and management of multi-storey dwelling blocks using large concrete panel systems

This exploratory study is concerned with the integrated appraisal of multi-storey dwelling blocks which incorporate large concrete panel systems (LPS). The first step was to look at U.K. multi-storey dwelling stock in general, and under the management of Birmingham City Council in particular. The information has been taken from the databases of three departments in the City of Birmingham, and rearranged in a new database using a suite of PC software called `PROXIMA' for clarity and analysis. One hundred of their stock were built large concrete panel system. Thirteen LPS blocks were chosen for the purpose of this study as case-studies depending mainly on the height and age factors of the block. A new integrated appraisal technique has been created for the LPS dwelling blocks, which takes into account the most physical and social factors affecting the condition and acceptability of these blocks. This appraisal technique is built up in a hierarchical form moving from the general approach to particular elements (a tree model). It comprises two main approaches; physical and social. In the physical approach, the building is viewed as a series of manageable elements and sub-elements to cover every single physical or environmental factor of the block, in which the condition of the block is analysed. A quality score system has been developed which depends mainly on the qualitative and quantitative conditions of each category in the appraisal tree model, and leads to physical ranking order of the study blocks. In the social appraisal approach, the residents' satisfaction and attitude toward their multi-storey dwelling block was analysed in relation to: a. biographical and housing related characteristics; and b. social, physical and environmental factors associated with this sort of dwelling, block and estate in general.The random sample consisted of 268 residents living in the 13 case study blocks. Data collected was analysed using frequency counts, percentages, means, standard deviations, Kendall's tue, r-correlation coefficients, t-test, analysis of variance (ANOVA) and multiple regression analysis. The analysis showed a marginally positive satisfaction and attitude towards living in the block. The five most significant factors associated with the residents' satisfaction and attitude in descending order were: the estate, in general; the service categories in the block, including heating system and lift services; vandalism; the neighbours; and the security system of the block. An important attribute of this method, is that it is relatively inexpensive to implement, especially when compared to alternatives adopted by some local authorities and the BRE. It is designed to save time, money and effort, to aid decision making, and to provide ranked priority to the multi-storey dwelling stock, in addition to many other advantages. A series of solution options to the problems of the block was sought for selection and testing before implementation. The traditional solutions have usually resulted in either demolition or costly physical maintenance and social improvement of the blocks. However, a new solution has now emerged, which is particularly suited to structurally sound units. The solution of `re-cycling' might incorporate the reuse of an entire block or part of it, by removing panels, slabs and so forth from the upper floors in order to reconstruct them as low-rise accommodations.

Statnote 24: Multiple regression

In previous statnotes, the application of correlation and regression methods to the analysis of two variables (X,Y) was described. These methods can be used to determine whether there is a linear relationship between the two variables, whether the relationship is positive or negative, to test the degree of significance of the linear relationship, and to obtain an equation relating Y to X. This Statnote extends the methods of linear correlation and regression to situations where there are two or more X variables, i.e., 'multiple linear regression’.

Gaussian process quantile regression using expectation propagation

Direct quantile regression involves estimating a given quantile of a response variable as a function of input variables. We present a new framework for direct quantile regression where a Gaussian process model is learned, minimising the expected tilted loss function. The integration required in learning is not analytically tractable so to speed up the learning we employ the Expectation Propagation algorithm. We describe how this work relates to other quantile regression methods and apply the method on both synthetic and real data sets. The method is shown to be competitive with state of the art methods whilst allowing for the leverage of the full Gaussian process probabilistic framework.

Factors determining disease duration in Alzheimer's disease:a postmortem study of 103 cases using the Kaplan-Meier estimator and Cox regression

Factors associated with duration of dementia in a consecutive series of 103 Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks-30 years, standard deviation = 5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration. © 2014 R. A. Armstrong.

Guiding local regression using visualisation

Solving many scientific problems requires effective regression and/or classification models for large high-dimensional datasets. Experts from these problem domains (e.g. biologists, chemists, financial analysts) have insights into the domain which can be helpful in developing powerful models but they need a modelling framework that helps them to use these insights. Data visualisation is an effective technique for presenting data and requiring feedback from the experts. A single global regression model can rarely capture the full behavioural variability of a huge multi-dimensional dataset. Instead, local regression models, each focused on a separate area of input space, often work better since the behaviour of different areas may vary. Classical local models such as Mixture of Experts segment the input space automatically, which is not always effective and it also lacks involvement of the domain experts to guide a meaningful segmentation of the input space. In this paper we addresses this issue by allowing domain experts to interactively segment the input space using data visualisation. The segmentation output obtained is then further used to develop effective local regression models.

Predicting class I major histocompatibility complex (MHC) binders using multivariate statistics:comparison of discriminant analysis and multiple linear regression

The accurate in silico identification of T-cell epitopes is a critical step in the development of peptide-based vaccines, reagents, and diagnostics. It has a direct impact on the success of subsequent experimental work. Epitopes arise as a consequence of complex proteolytic processing within the cell. Prior to being recognized by T cells, an epitope is presented on the cell surface as a complex with a major histocompatibility complex (MHC) protein. A prerequisite therefore for T-cell recognition is that an epitope is also a good MHC binder. Thus, T-cell epitope prediction overlaps strongly with the prediction of MHC binding. In the present study, we compare discriminant analysis and multiple linear regression as algorithmic engines for the definition of quantitative matrices for binding affinity prediction. We apply these methods to peptides which bind the well-studied human MHC allele HLA-A*0201. A matrix which results from combining results of the two methods proved powerfully predictive under cross-validation. The new matrix was also tested on an external set of 160 binders to HLA-A*0201; it was able to recognize 135 (84%) of them.

Quantitative prediction of mouse class I MHC peptide binding affinity using support vector machine regression (SVR) models

Background - The binding between peptide epitopes and major histocompatibility complex proteins (MHCs) is an important event in the cellular immune response. Accurate prediction of the binding between short peptides and the MHC molecules has long been a principal challenge for immunoinformatics. Recently, the modeling of MHC-peptide binding has come to emphasize quantitative predictions: instead of categorizing peptides as "binders" or "non-binders" or as "strong binders" and "weak binders", recent methods seek to make predictions about precise binding affinities. Results - We developed a quantitative support vector machine regression (SVR) approach, called SVRMHC, to model peptide-MHC binding affinities. As a non-linear method, SVRMHC was able to generate models that out-performed existing linear models, such as the "additive method". By adopting a new "11-factor encoding" scheme, SVRMHC takes into account similarities in the physicochemical properties of the amino acids constituting the input peptides. When applied to MHC-peptide binding data for three mouse class I MHC alleles, the SVRMHC models produced more accurate predictions than those produced previously. Furthermore, comparisons based on Receiver Operating Characteristic (ROC) analysis indicated that SVRMHC was able to out-perform several prominent methods in identifying strongly binding peptides. Conclusion - As a method with demonstrated performance in the quantitative modeling of MHC-peptide binding and in identifying strong binders, SVRMHC is a promising immunoinformatics tool with not inconsiderable future potential.

General Regression Neuro–Fuzzy Network for Identification of Nonstationary Plants

General Regression Neuro-Fuzzy Network, which combines the properties of conventional General Regression Neural Network and Adaptive Network-based Fuzzy Inference System is proposed in this work. This network relates to so-called “memory-based networks”, which is adjusted by one-pass learning algorithm.