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Yesterday I learned something interesting from a talk given by Professor Bikas K Sinha. The following is an excerpt from the reference [1], which exactly shows the interesting point of the problem.
“A population consisting of an unknown number of distinct species is searched by selecting one member at a time. No a priori information is available concerning the probability that an object selected from this population will represent a particular species. Based on the information available after an nstage search it is desired to predict the conditional probability that the next selection will represent a species not represented in the nstage sample.”
Searcher: “I am contemplating extending my initial search an additional m stages, and will so do if the expected number of individuals I will select in the second search who are new species is large. What do you recommend?”
Statistician: “Make one more search and then I will tell you.”
Refer to the Annals of Statistics paper:
[1] Starr, Norman. “Linear estimation of the probability of discovering a new species.” The Annals of Statistics (1979): 644652.
Recently I was referred to a nice article talking about the relationship between Statistics and data science. Here is my feedback to share with you:
 First of all, Statistics is a science dealing with data, including five main components, data collection (design of experiment, sampling), data preparation (storage, reading, organization, cleaning), exploratory data analysis (numerical summarization, visualization), statistical inference (frequentist and Bayesian) and communication (interpretation).
 It’s statistician’s mistake putting extremely unequal weights on the development of the five components in the past 50 years, mostly focusing on the fourth component.
 Fortunately, the first component is now showing resurgence under the massive data situation. How to sample the “influential” data points from massive samples is a big and important research topic.
 People outside of traditional statistics community have been picking up the second and third components, like adopting the two undeveloped statistics children. And the adoptive parents are saying that the two children are not statistics, and instead they call them data science.
 But Statistics is really about all of the five equally important components.
 And our Statistician’s goal is to get the two children back to our statistics community. We are all Statistician!
 Deep Learning Master Class
 Advances in Variational Inference
 Numerical Optimization: Understanding LBFGS
 An exact mapping between the Variational Renormalization Group and Deep Learning
 New ASA Guidelines for Undergraduate Statistics Programs
 奇异值分解（We Recommend a Singular Value Decomposition）
 如何简单形象又有趣地讲解神经网络是什么？
 Academic vs. Industry Careers
 Hadley Wickham: Impact the world by being useful
 Statisticians in World War II: They also served
 A Brief Overview of Deep Learning
 Advice for applying Machine Learning
 Deep Learning Tutorial
 Gibbs Sampling in Haskell
 Howto go parallel in R – basics + tips
The first colloquium speaker at this semester, professor Wei Zheng from IUPUI, will give a talk on “Universally optimal designs for two interference models“. In this data explosive age, people are easy to get big data set, which renders people difficult to make inferences from such massive data. Since people usually think that with more data, they have more chance to get more useful information from them, lots of researchers are struggling to achieve methodological advancements under this setup. This is a very challenging research area and of course very important, which in my opinion needs the resurgence of mathematical statistics by borrowing great ideas from various mathematical fields. However, another great and classical statistical research area should come back again to help statistical inference procedures from the beginning stage of data analysis, collecting data by design of experiments so that we can control the data quality, usefulness and size. Thus it’s necessary for us to know what is optimal design of experiments. Here is an introduction to this interesting topic.
In statistics, we have to organize an experiment in order to gain some information about an object of interest. Fragments of this information can be obtained by making observations within some elementary experiments called trials. The set of all trials which can be incorporated in a prepared experiment will be denoted by , which we shall call the design space. The problem to be solved in experimental design is how to choose, say trials , called the support points of the design, or eventually how to choose the size of the design, to gather enough information about the object of interest. Optimum experimental design corresponds to the maximization, in some sense, of this information. In specific, the optimality of a design depends on the statistical model and is assessed with respect to a statistical criterion, which is related to the variancematrix of the estimator. Specifying an appropriate model and specifying a suitable criterion function both require understanding of statistical theory and practical knowledge with designing experiments.
We shall restrict our attention to the parametric situation in the case of a regression model, the mean response function is then parameterized as
specifying for a particular with unknown parameter .
A design is specified by an initially arbitrary measure assigning design points to estimate the parameter vector. Here can be written as
where the design support points are elements of the design space , and the associated weights are nonnegative real numbers which sum to one. We make the usual second moment error assumptions leading to the use of least squares estimates. Then the corresponding Fisher information matrix associated with is given by
where and .
Now we have to propose the statistical criteria for the optimum. It is known that the least squares estimator minimizes the variance of meanunbiased estimators (under the conditions of the Gauss–Markov theorem). In the estimation theory for statistical models with one real parameter, the reciprocal of the variance of an (“efficient”) estimator is called the “Fisher information” for that estimator. Because of this reciprocity, minimizing the variance corresponds to maximizing the information. When the statistical model has several parameters, however, the mean of the parameterestimator is a vector and its variance is a matrix. The inverse matrix of the variancematrix is called the “information matrix”. Because the variance of the estimator of a parameter vector is a matrix, the problem of “minimizing the variance” is complicated. Using statistical theory, statisticians compress the informationmatrix using realvalued summary statistics; being realvalued functions, these “information criteria” can be maximized. The traditional optimalitycriteria are invariants of the information matrix; algebraically, the traditional optimalitycriteria are functionals of the eigenvalues of the information matrix.
 Aoptimality (“average” or trace)
 One criterion is Aoptimality, which seeks to minimize the trace of the inverse of the information matrix. This criterion results in minimizing the average variance of the estimates of the regression coefficients.
 Doptimality (determinant)
 A popular criterion is Doptimality, which seeks to maximize the determinant of the information matrix of the design. This criterion results in maximizing the differential Shannon information content of the parameter estimates.
 Eoptimality (eigenvalue)
 Another design is Eoptimality, which maximizes the minimum eigenvalue of the information matrix.
 Toptimality
 This criterion maximizes the trace of the information matrix.
Other optimalitycriteria are concerned with the variance of predictions:
 Goptimality
 A popular criterion is Goptimality, which seeks to minimize the maximum entry in the diagonal of the hat matrix. This has the effect of minimizing the maximum variance of the predicted values.
 Ioptimality (integrated)
 A second criterion on prediction variance is Ioptimality, which seeks to minimize the average prediction variance over the design space.
 Voptimality (variance)
 A third criterion on prediction variance is Voptimality, which seeks to minimize the average prediction variance over a set of m specific points.
Now back to our example, because the asymptotic covariance matrix associated with the LSE of is proportional to , the most popular regression design criterion is Doptimality, where designs are sought to minimize the determinant of . And the standardized predicted variance function, corresponding to the Goptimality, is
and Goptimality seeks to minimize .
A central result in the theory of optimal design, the General Equivalence Theorem, asserts that the design that is Doptimal is also Goptimal and that
the number of parameters.
Now the optimal design for an interference model, professor Wei Zheng will talk about, considers the following model in the block designs with neighbor effects:
where is the treatment assigned to the plot in the th position of the th block, and
 is the general mean;
 is the direct effect of treatment ;
 and are respectively the left and right neighbor effects; that’s the interference effect of the treatment assigned to, respectively, the left and right neighbor plots and .
 is the effect of the th block; and
 is the random error, .
We seed the optimal design among designs , the set of all designs with blocks of size and with treatments.
I am not going into the details of the derivation of the optimal design for the above interference model. I just sketch the outline here. First of all we can write down the information matrix for the direct treatment effect , say . Let be the set of all possible block sequences with replacement, which is the design space. Then we try to find the optimal measure among the set to maximize for a given function satisfying the following three conditions:
 is concave;
 for any permutation matrix ;
 is nondecreasing in the scalar .
A measure which achieves the maximum of among for any satisfying the above three conditions is said to be universally optimal. Such measure is optimal under criteria of A, D, E, T, etc. Thus we could imagine that all of the analysis is just linear algebra.
There has been a Machine Learning (ML) reading list of books in hacker news for a while, where Professor Michael I. Jordan recommend some books to start on ML for people who are going to devote many decades of their lives to the field, and who want to get to the research frontier fairly quickly. Recently he articulated the relationship between CS and Stats amazingly well in his recent reddit AMA, in which he also added some books that dig still further into foundational topics. I just list them here for people’s convenience and my own reference.
 Frequentist Statistics
 Casella, G. and Berger, R.L. (2001). “Statistical Inference” Duxbury Press.—Intermediatelevel statistics book.
 Ferguson, T. (1996). “A Course in Large Sample Theory” Chapman & Hall/CRC.—For a slightly more advanced book that’s quite clear on mathematical techniques.
 Lehmann, E. (2004). “Elements of LargeSample Theory” Springer.—About asymptotics which is a good starting place.
 Vaart, A.W. van der (1998). “Asymptotic Statistics” Cambridge.—A book that shows how many ideas in inference (M estimation, the bootstrap, semiparametrics, etc) repose on top of empirical process theory.
 Tsybakov, Alexandre B. (2008) “Introduction to Nonparametric Estimation” Springer.—Tools for obtaining lower bounds on estimators.
 B. Efron (2010) “LargeScale Inference: Empirical Bayes Methods for Estimation, Testing, and Prediction” Cambridge,.—A thoughtprovoking book.
 Bayesian Statistics
 Gelman, A. et al. (2003). “Bayesian Data Analysis” Chapman & Hall/CRC.—About Bayesian.
 Robert, C. and Casella, G. (2005). “Monte Carlo Statistical Methods” Springer.—about Bayesian computation.
 Probability Theory
 Grimmett, G. and Stirzaker, D. (2001). “Probability and Random Processes” Oxford.—Intermediatelevel probability book.
 Pollard, D. (2001). “A User’s Guide to Measure Theoretic Probability” Cambridge.—More advanced level probability book.
 Durrett, R. (2005). “Probability: Theory and Examples” Duxbury.—Standard advanced probability book.
 Optimization
 Bertsimas, D. and Tsitsiklis, J. (1997). “Introduction to Linear Optimization” Athena.—A good starting book on linear optimization that will prepare you for convex optimization.
 Boyd, S. and Vandenberghe, L. (2004). “Convex Optimization” Cambridge.
 Y. Nesterov and Iu E. Nesterov (2003). “Introductory Lectures on Convex Optimization” Springer.—A start to understand lower bounds in optimization.
 Linear Algebra
 Golub, G., and Van Loan, C. (1996). “Matrix Computations” Johns Hopkins.—Getting a full understanding of algorithmic linear algebra is also important.
 Information Theory
 Cover, T. and Thomas, J. “Elements of Information Theory” Wiley.—Classic information theory.
 Functional Analysis
 Kreyszig, E. (1989). “Introductory Functional Analysis with Applications” Wiley.—Functional analysis is essentially linear algebra in infinite dimensions, and it’s necessary for kernel methods, for nonparametric Bayesian methods, and for various other topics.
Remarks from Professor Jordan: “not only do I think that you should eventually read all of these books (or some similar list that reflects your own view of foundations), but I think that you should read all of them three times—the first time you barely understand, the second time you start to get it, and the third time it all seems obvious.”
In mathematics, a general principle for studying an object is always from the study of the object itself to the study of the relationship between objects. In functional data analysis, the most important part for studying of the object itself, i.e. one functional data set, is functional principal component analysis (FPCA). And for the study of the relationship between two functional data sets, one popular way is various types of regression analysis. For this post, I only focus on the FPCA. The central idea of FPCA is dimension reduction by means of a spectral decomposition of the covariance operator, which yields functional principal components as coefficient vectors to represent the random curves in the sample.
First of all, let’s define what’s the FPCA. Suppose we observe functions . We want to find an orthonormal basis such that
is minimized. Once such a basis is found, we can replace each curve by to a good approximation. This means instead of working with infinitely dimensional curves , we can work with $K$dimensional vectors . And the functions are called collectively optimal empirical orthonormal basis, or empirical functional principal components. Note that once we got the functional principal components, we can get the so called FPC scores to approximate the curves.
For FPCA, we usually adopt the so called “smoothfirstthenestimate” approach, namely,we first preprocess the discrete observations to get smoothed functional data by smoothing and then use the empirical estimators of the mean and covariance based on the smoothed functional data to conduct FPCA.
For the smoothing step, we have to consider individual by individual. For each realization, we can use basis expansion (Polynomial basis is unstable; Fourier basis is suitable for periodic functions; Bspline basis is flexible and useful), smoothing penalties (which lead to smoothing splines by the Smoothing Spline Theorem), as well as local polynomial smoothing:
 Basis expansion: by assuming one realization of the underlying true process , where are the basis functions, we have the estimation
 Smoothing penalties: , where is a measure for the roughness of functions.
 Local linear smoothing: assume at point , we have , then we have estimated by the following
Once we have the smoothed functional data, denoted as , we can have the empirical estimator of the mean and covariance as
And then we can have the empirical functional principal components as the eigenfunctions of the above sample covariance operator (for the proof, refer to the book “Inference for Functional Data with Applications” page 39). Note that the above estimation procedure of the mean function and the covariance function need to have more dense functional data, since otherwise the smoothing step will be not stable. Thus people are also proposing some other estimators of mean function and covariance function, such as the local linear estimator for the mean function and the covariance function proposed by Professor Yehua Li from ISU, which has an advantage that they can cover all types of functional data, sparse (i.e. longitudinal), dense, or inbetween. Now the problem is that how to conduct FPCA based on in practice. Actually it’s the following classic mathematical problem:
where is the integral operator with a symmetric kernel . This is a wellstudied problem in computing the eigenvalues and eigenfunctions of an integral operator with a symmetric kernel in applied mathematics. So people can refer to those numerical methods to solve the above problem.
However, two common methods used in Statistics are described in Section 8.4 in the fundamental functional data analysis book written by Professors J. O. Ramsay and B. W. Silverman. One is the discretizing method and the other is the basis function method. For the discretizing method, essentially, we just discretize the smoothed functions to a fine grid of equally spaced values that span the interval, and then use the traditional PCA, followed by some interpolation method for other points not belonging to be selected grid points. Now for the basis function method, we illustrate it by assuming the mean function equal to 0:
 Basis expansion: , and then , where and ;
 Covariance function: ;
 Eigenfunction expansion: assume the eigenfunction ;
 Problem Simplification: The above basis expansions lead to
,
where and . Hence the eigen problem boils down to , which is equivalent to
Note that the assumptions for the eigenfunctions to be orthonormal are equivalent to . Let , and then we have the above problem as
which is a traditional eigen problem for symmetric matrix .
Two special cases deserve particular attention. One is orthonormal basis which leads to . And the other is taking the smoothed functional data as the basis function which leads to .
Note that the empirical functional principal components are proved to be the eigenfunctions of the sample covariance operator. This fact connects the FPCA with the so called KarhunenLove expansion:
where are uncorrelated random variables with mean 0 and variance $\lambda_k$ where . For simplicity we assume . Then we can easily see the connection between KL expansion and FPCA. is the series of orthonormal basis functions, and are those FPC scores.
So far, we only have discussed how to get the empirical functional principal components, i.e. eigenfunctions/orthonormal basis functions. But to represent the functional data, we have to get those coefficients, which are called FPC scores . The simplest way is by numerical integration:
Note that for the above estimation of the FPC scores via numerical integration, we first need the smoothed functional data . So if we only have sparsely observed functional data, this method will not provide reasonable approximations. Professor Fang Yao et al. proposed the so called PACE (principal component analysis through conditional expectation) to deal with such longitudinal data.
Degrees of freedom and information criteria are two fundamental concepts in statistical modeling, which are also taught in introductory statistics courses. But what are the exact abstract definitions for them which can be used to derive specific calculation formula in different situations.
I often use fit criteria like AIC and BIC to choose between models. I know that they try to balance good fit with parsimony, but beyond that I’m not sure what exactly they mean. What are they really doing? Which is better? What does it mean if they disagree? — Signed, Adrift on the IC’s
Intuitively, the degrees of freedom of a fitting procedure reflects the effective number of parameters used by the fitting procedure. Thus to most applied statisticians, a fitting procedure’s degrees of freedom is synonymous with its model complexity, or its capacity for overfitting to data. Is this really true? Regularization aims to improve prediction performance by trading an increase in training error for better agreement between training and prediction errors, which is often captured through decreased degrees of freedom. Is this always the case? When does more regularization imply fewer degrees of freedom?
For the above two questions, I think the most important thing is based on the following whattype question:
What are AIC and BIC? What is degrees of freedom?
Akaike’s Information Criterion (AIC) estimates the relative KullbackLeibler (KL) distance of the likelihood function specified by a fitted candidate model, from the unknown true likelihood function that generated the data:
where is the likelihood function specified by a fitted candidate model, is the unknown true likelihood function, and the expectation is taking under the true model. Note that the fitted model closest to the truth in the KL sense would not necessarily be the model which best fits the observed sample since the observed sample can often be fit arbitrary well by making the model more and more complex. Since will be the same for all models being considered, KL is minimized by choosing the model with highest , which can be estimated by an approximately unbiased estimator (up to a constant)
where is an estimator for the covariance matrix of the parameters based on the second derivatives matrix of in the parameters and is an estimator based on the cross products of the first derivatives. Akaike showed that and are asymptotically equal for the true model, so that , which is the number of parameters. This results in the usual definition for AIC
Schwarz’s Bayesian Information Criterion (BIC) is just comparing the posterior probability with the same prior and hence just comparing the likelihoods under different models:
which is just the Bayes factor. Schwarz showed that in many kinds of models can be roughly approximated by
which leads to the definition of BIC
In summary, AIC and BIC are both penalizedlikelihood criteria. AIC is an estimate of a constant plus the relative distance between the unknown true likelihood function of the data and the fitted likelihood function of the model, so that a lower AIC means a model is considered to be closer to the truth. BIC is an estimate of a function of the posterior probability of a model being true, under a certain Bayesian setup, so that a lower BIC means that a model is considered to be more likely to be the true model. Both criteria are based on various assumptions and asymptotic approximations. Despite various subtle theoretical differences, their only difference in practice is the size of the penalty; BIC penalizes model complexity more heavily. The only way they should disagree is when AIC chooses a larger model than BIC. Thus, AIC always has a chance of choosing too big a model, regardless of n. BIC has very little chance of choosing too big a model if n is sufficient, but it has a larger chance than AIC, for any given n, of choosing too small a model.
The effective degrees of freedom for an arbitrary modelling approach is defined based on the concept of expected optimism:
where is the variance of the error term, is an independent copy of data vector with mean , and is a fitting procedure with tuning parameter . Note that the expected optimism is defined as . And by the optimism theorem, we have that
Why does this definition make sense? In fact, under some regularity conditions, Stein proved that
which can be regarded as a sensitivity measure of the fitted values to the observations.
In the linear model, we know that (Mallows) the relationship between the expected prediction error (EPE) and the residual sum of squares (RSS) follows
which leads to .
Here are some references on this topic:

Dziak, John J., et al. “Sensitivity and specificity of information criteria.” The Methodology Center and Department of Statistics, Penn State, The Pennsylvania State University (2012).

Janson, Lucas, Will Fithian, and Trevor Hastie. “Effective degrees of freedom: A flawed metaphor.” arXiv preprint arXiv:1312.7851 (2013).
Recently some papers discussed in our journal club are focused on integrative clustering of multiple omics data sets. I found that they are all originated from factor analysis and make use of the advantage of factor analysis over principal component analysis.
Let’s recall the model for factor analysis:
where () and , with mean and loading matrix fixed, and factors with diagonal. And we also assume that and are uncorrelated. Note that this model is just characterizing the covariance structure of the Gaussian random vector . Now we need to think about the roles of the loading matrix and factors. In fact, we can think about this model in the following way: if we are given such a random vector, then is just what you see of this random vector in one coordinate system under which the components of are correlated; but if you look at the random vector in another coordinate system which is a linear transformation () of the original coordinate system, then you will see , whose components are uncorrelated. That is, the randomness in and is the same but with different views. With the observed sample with sample size ,
we can use the EM algorithm to get the MLE of the parameters (note that you will find maximizing the likelihood directly is hard).
Now for principal component analysis, for clarity, we are going to differentiate the classical (nonprobabilistic) principal component analysis and probabilistic principal component analysis. The classical principal component analysis actually has no statistical model. And the probabilistic principal component model is defined as the above factor analysis model with and is orthonormal. And people can show that as , it becomes the classical principal component analysis. Actually we know that PCA maximizes data variance captured by the low dimensional projection, or equivalently minimizes the reconstruction error under the norm of the projected data points with the original data, namely
where here is the data matrix, and . And we know that solution to this problem is through SVD of the sample covariance: contains the eigenvectors corresponding to the largest eigenvalues. And are the projected data points. From this analysis, we could see that the difference between factor analysis and the classical principal component analysis is that PCA treats covariance and variance identically, while factor analysis is trying to model to covariance and variance separately. In fact, the principal components are chosen to capture as much variance as possible, but the latent variables in a factor analysis model are chosen to explain as much covariance as possible. (Note that all the correlations amongst the variables must be explained by the common factors; if we assume joint normality the observed variables will be conditionally independent given .)
In applications, we just deal with the data matrix, . And the loadings of the first principal component, as a vector, denoted as , is a normalized vector, i.e. , which makes have the largest variance. And we call as the first principal component score vector. In the common R package “prcomp” for the principal component analysis, the following command out=prcomp(X, scale=TRUE), can give us the loading matrix by referring to out$rotation, and the score matrix by referring to out$x. That is the loading matrix is and the score matrix is , which is the realizations of the factors .
Now think about what is the difference between the factor analysis and the probabilistic principal component analysis (PPCA). From the above definition, we see that the main difference is that factor analysis allow individual characteristics through the error term by instead of . In this perspective, we have
with common structure across all components of and individual characteristics . While PPCA does not allow any individual characteristics by assuming for all . This essential difference will make factor analysis more useful in integrative data analysis since it has more flexibility.
The AOAS 2013 paper is exactly using the above idea for modeling the integrative clustering:
where with data sources. By stacking all the data sources together, we have
which is exactly a simple factor analysis. And this factor analysis model is more useful than PCA in this data integration setup just due to the allowing of individual characteristics for different data sources through . And their paper is also dealing with sparsity in .
The 2014 arXived paper is just generalizing the above paper by allowing another layer of individual characteristis:
But the problem for this one is how to do the estimation. Instead of using EM algorithm as used in the AOAS 2013 paper, they used the one as in the PCA by minimizing the reconstruction error.
On this Tuesday, Professor Xuming He presented their recent work on subgroup analysis, which is very interesting and useful in reality. Think about the following very much practical problem (since the drug is expensive or has certain amount of side effect):
If you are given the drug response, some baseline covariates which have nothing to do with the treatment, and the treatment indicator as well as some posttreatment measurements, how could you come up with a statistical model to tell whether there exist subgroups which respond to the treatment differently?
Think about 5 minutes and continue the following!
Dr He borrowed a very traditional model in Statistics, logisticnormal mixture model to study the above problem. The existence of the two subgroups is characterized by the observed baseline covariates, which have nothing to do with the treatment:
where is the unobserved membership index. And the observed response follows a normal mixture model
with different means and , where usually contains but also includes the treatment indicator as well as any posttreatment measurements. Given that there is two subgroups characterized by the baseline covariates (which makes the test problem regular), they tried to test whether the two groups respond to the treatment differently, that is testing the component of which corresponds to the treatment indicator.
Nice work to demonstrate how to come up with a statistical model to study some interesting and practical problems!
But the above part has nothing to do with the title, EM algorithm. Actually you could imagine that they will use EM as a basic tool to study the above mixture model. That’s why I came back to revisit this great idea in Statistics.
Given complete random vector with observed and unobserved, we have the likelihood function . Then the log marginal likelihood has the following property:
where the last inequality is from Jensen’s inequality, and is any density function put on . In order to make the bound tight, i.e. to make the above inequality as equality, one possible way is , which leads to
Then we have
In summary, we have the following EM procedure:
 E step: get the conditional distribution ;
 M step:
And the corresponding EM algorithm can be described as the following iterative procedure:
 E step: get the conditional distribution ;
 M step:
In order to make this procedure effective, in the M step, the condition expectation should be easy to calculate. In fact, usually, since the expectation will be taken under the current , which will not produce any new , we usually get first and then by plugging we have .
And this procedure guarantees the following to make sure the convergence
In summary, EM algorithm is useful when the marginal problem is difficult while the joint problem is easy. However is unobservable, and the EM algorithm attempts to maximize iteratively, by replacing it with its conditional expectation given the observed data. This expectation is computed with respect to the distribution of the complete data evaluated at the current estimate of .
In the talk given by Professor Xuming He, he mentioned a rule of thumb from practice experience that the EM algorithm produces a good enough estimator in the first few steps.
Last night, I had a discussion about the integrative data analysis (closely related with the discussion of AOAS 2014 paper from Dr Xihong Lin’s group and JASA 2014 paper from Dr. Hongzhe Li’s group) with my friend. If some biologist gave you the genetic variants (e.g. SNP) data and the phenotype (e.g. some trait) data, you were asked to do the association analysis to identify the genetic variants which is significantly associated with the trait. One year later, the biologist got some additional data such as gene expression data which are related with the two data sets given before, and you are now asked to calibrate your analysis to detect the association more efficiently and powerfully by integrating the three data sources. In this data rich age, it’s quite natural to get into this situation in practice. The question is how to come up with a natural and useful statistical framework to deal with such data integration.
For simplicity, we considered the problem that if you are first given two random variables, to study the association between them. Later on you are given another random variable to help to detect the significance association between and . We assume the following true model:
where is independent with . Now the question is what is the characteristic for to be helpful to raise the power for the detection.
 What if and are uncorrelated? If they are uncorrelated, then what if and are uncorrelated?
 What if and are correlated?
After thinking about these, you will find that for to be useful, it’s ideal that is uncorrelated with and is highly correlated with , i.e. highly correlated with the error term so that it can be used to explain more variation contained in to reduce the noise level.
In order to see why, first notice that the problem exactly depends on how to understand the following multiple linear regression problem:
Now from the multiple linear regression knowledge, we have
where (see below for the proof). Thus in order to raise the signal to noise ratio, we hope that , i.e. or , which can keep the signal large. But in order to reduce the noise, we need . In summary, we need to have , which means that and are uncorrelated, and , which means that can be used to explain some variability contained in the noise.
Now please think about the question:
What is the difference between doing univariate regression one by one and doing multiple linear regression all at once?
Here is some hint: first we regress and both onto ,
And then on one hand we find that , and on the other hand we regress the residual onto the residual to get via
This procedure actually is explaining what is the multiple linear regression and what is the meaning for the coefficients (think about the meaning of from the above explanation).
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