arXiv subjects

Kanti V. Mardia

Publications and source records attributed to Kanti V. Mardia.

At least 19 recordsLinked to original sources

arXiv2026

AlphaFold's Bayesian Roots in Probability Kinematics

The seminal breakthrough of AlphaFold in protein structure prediction relied on a learned potential energy function parameterized by deep models, in contrast to its successors AlphaFold2 and AlphaFold3, which lack an explicit probabilistic interpretation. While AlphaFold's potential was originally justified by heuristic analogy to physical potentials of mean force, we show that it can instead be understood as a principled instance of probability kinematics (PK), also known as Jeffrey conditioning, a generalization of Bayesian updating. This reinterpretation reveals that AlphaFold is a generalized Bayesian model that explicitly defines a posterior distribution over structures, providing a deeper explanation of its success and a foundation for future model design. To demonstrate this framework with precision, we introduce a tractable synthetic model in which an angular random walk prior is updated with distance-based evidence via PK, directly mirroring AlphaFold's mechanism. This setting allows us to explore the probabilistic foundations of AlphaFold in a clear and interpretable way. Our work connects a landmark in protein structure prediction to a broader class of compositional deep generative models and points to new opportunities for principled probabilistic approaches.

cs.LG↗

arXiv2026

A Cylindrical Galton Board at the Galton Board's 150th Anniversary

The Galton board is a well known device for showing how repeated Bernoulli trials on a triangular lattice produce an approximately normal distribution. Marking the 150th anniversary of Galton's 1875 construction, this paper revisits the original apparatus and extends it to a cylindrical setting in which the peg lattice is wrapped around a cylinder. This creates angular periodicity and leads to height dependent behaviour that does not arise in the classical planar design. The cylindrical form links Galton's demonstration of variation and the emergence of the normal distribution with modern ideas in circular statistics, giving a physical realisation of binomial random walks on a circular linear product space. We distinguish cases where the wrapped lattice covers only an arc from those that span the full circumference, and show how these geometries lead to wrapped binomial and wrapped normal behaviour. We describe the construction of our physical model, discuss practical issues for replication, and analyse its statistical and pedagogical properties as a modern reinterpretation of Galton's work.

stat.OT↗

arXiv2026

The projected isotropic normal distribution with applications in neuroscience

This paper is motivated by a cutting-edge application in neuroscience: the analysis of electroencephalogram (EEG) signals recorded under flash stimulation. Under commonly used signal-processing assumptions, only the phase angle of the EEG is required for the analysis of such applications. We demonstrate that these assumptions imply that the phase has a projected isotropic normal distribution. We revisit this distribution and derive several new properties, including closed-form expressions for its trigonometric moments. We then examine the distribution of the mean resultant and its square -- a statistic of central importance in phase-based EEG studies. The distribution of the resultant is analytically intricate; to make it practically useful, we develop two approximations based on the well-known resultant distribution for the von Mises distribution. We then study inference problems for this projected isotropic normal distribution. The method is illustrated with an application to EEG data from flash-stimulation experiments.

stat.ME↗

arXiv2026

Asymmetry Analysis of Bilateral Shapes

Many biological objects possess bilateral symmetry about a midline or midplane, up to a ``noise'' term. This paper uses landmark-based methods to measure departures from bilateral symmetry, especially for the two-group problem where one group is more asymmetric than the other. In this paper, we formulate our work in the framework of size-and-shape analysis including registration via rigid body motion. Our starting point is a vector of elementary asymmetry features defined at the individual landmark coordinates for each object. We introduce two approaches for testing. In the first, the elementary features are combined into a scalar composite asymmetry measure for each object. Then standard univariate tests can be used to compare the two groups. In the second approach, a univariate test statistic is constructed for each elementary feature. The maximum of these statistics lead to an overall test statistic to compare the two groups and we then provide a technique to extract the important features from the landmark data. Our methodology is illustrated on a pre-registered smile dataset collected to assess the success of cleft lip surgery on human subjects. The asymmetry in a group of cleft lip subjects is compared to a group of normal subjects, and statistically significant differences have been found by univariate tests in the first approach. Further, our feature extraction method leads to an anatomically plausible set of landmarks for medical applications.

stat.ME↗

arXiv2025

Modelling toroidal and cylindrical data via the trivariate wrapped Cauchy copula with non-uniform marginals

In this paper, we propose a new flexible family of distributions for data that consist of three angles, two angles and one linear component, or one angle and two linear components. To achieve this, we equip the recently proposed trivariate wrapped Cauchy copula with non-uniform marginals and develop a parameter estimation procedure. We compare our model to its main competitors for analyzing trivariate data and provide some evidence of its advantages. We illustrate our new model using toroidal data from protein bioinformatics of conformational angles, and cylindrical data from climate science related to buoy in the Adriatic Sea. The paper is motivated by these real trivariate datasets.

stat.ME↗

arXiv2025

The trivariate wrapped Cauchy copula

In this paper, we propose a new flexible distribution for data on the three-dimensional torus which we call a trivariate wrapped Cauchy copula. Our trivariate copula has several attractive properties. It has a simple form of density and desirable modality properties. Its parameters allow for an adjustable degree of dependence between every pair of variables and these can be easily estimated. The conditional distributions of the model are well studied bivariate wrapped Cauchy distributions. Furthermore, the distribution can be easily simulated. Parameter estimation via maximum likelihood for the distribution is given and we highlight the simple implementation procedure to obtain these estimates. We illustrate our trivariate wrapped Cauchy copula on data from protein bioinformatics of conformational angles.

stat.ME↗

arXiv2025

Constrained Shape Analysis with Applications to RNA Structure

In many applications of shape analysis, lengths between some landmarks are constrained. For instance, biomolecules often have some bond lengths and some bond angles constrained, and variation occurs only along unconstrained bonds and constrained bonds' torsions where the latter are conveniently modelled by dihedral angles. Our work has been motivated by low resolution biomolecular chain RNA where only some prominent atomic bonds can be well identified. Here, we propose a new modelling strategy for such constrained shape analysis starting with a product of polar coordinates (polypolars), where, due to constraints, for example, some radial coordinates should be omitted, leaving products of spheres (polyspheres). We give insight into these coordinates for particular cases such as five landmarks which are motivated by a practical RNA application. We also discuss distributions for polypolar coordinates and give a specific methodology with illustration when the constrained size-and-shape variables are concentrated. There are applications of this in clustering and we give some insight into a modified version of the MINT-AGE algorithm.

stat.ME↗

arXiv2024

Fisher's Legacy of Directional Statistics, and Beyond to Statistics on Manifolds

It will not be an exaggeration to say that R A Fisher is the Albert Einstein of Statistics. He pioneered almost all the main branches of statistics, but it is not as well known that he opened the area of Directional Statistics with his 1953 paper introducing a distribution on the sphere which is now known as the Fisher distribution. He stressed that for spherical data one should take into account that the data is on a manifold. We will describe this Fisher distribution and reanalyse his geological data. We also comment on the two goals he set himself in that paper, and how he reinvented the von Mises distribution on the circle. Since then, many extensions of this distribution have appeared bearing Fisher's name such as the von Mises Fisher distribution and the matrix Fisher distribution. In fact, the subject of Directional Statistics has grown tremendously in the last two decades with new applications emerging in Life Sciences, Image Analysis, Machine Learning and so on. We give a recent new method of constructing the Fisher type distribution which has been motivated by some problems in Machine Learning. The subject related to his distribution has evolved since then more broadly as Statistics on Manifolds which also includes the new field of Shape Analysis. We end with a historical note pointing out some correspondence between D'Arcy Thompson and R A Fisher related to Shape Analysis.

stat.ME↗

arXiv2023

Fisher's Pioneering work on Discriminant Analysis and its Impact on AI

Fisher opened many new areas in Multivariate Analysis, and the one which we will consider is discriminant analysis. Several papers by Fisher and others followed from his seminal paper in 1936 where he coined the name discrimination function. Historically, his four papers on discriminant analysis during 1936-1940 connect to the contemporaneous pioneering work of Hotelling and Mahalanobis. We revisit the famous iris data which Fisher used in his 1936 paper and in particular, test the hypothesis of multivariate normality for the data which he assumed. Fisher constructed his genetic discriminant motivated by this application and we provide a deeper insight into this construction; however, this construction has not been well understood as far as we know. We also indicate how the subject has developed along with the computer revolution, noting newer methods to carry out discriminant analysis, such as kernel classifiers, classification trees, support vector machines, neural networks, and deep learning. Overall, with computational power, the whole subject of Multivariate Analysis has changed its emphasis but the impact of this Fisher's pioneering work continues as an integral part of supervised learning in Artificial Intelligence.

stat.ME↗

arXiv2022

Families of discrete circular distributions with some novel applications

Motivated by some cutting edge circular data such as from Smart Home technologies and roulette spins from online and casino, we construct some new rich classes of discrete distributions on the circle. We give four new general methods of construction, namely (i) maximum entropy, (ii) centered wrapping, (iii) marginalized and (iv) conditionalized methods. We motivate these methods on the line and then work on the circular case and provide some properties to gain insight into these constructions. We mainly focus on the last two methods (iii) and (iv) in the context of circular location families, as they are amenable to general methodology. We show that the marginalized and conditionalized discrete circular location families inherit important properties from their parent continuous families. In particular, for the von Mises and wrapped Cauchy as the parent distribution, we examine their properties including the maximum likelihood estimators, the hypothesis test for uniformity and give a test of serial independence. Using our discrete circular distributions, we demonstrate how to determine changepoint when the data arise in a sequence and how to fit mixtures of this distribution. Illustrative examples are given which triggered the work. For example, for roulette data, we test for uniformity (unbiasedness) , test for serial correlation, detect changepoint in streaming roulette-spins data, and fit mixtures. We analyse a smart home data using our mixtures. We examine the effect of ignoring discreteness of the underlying population, and discuss marginalized versus conditionalized approaches. We give various extensions of the families with skewness and kurtosis, to those supported on an irregular lattice, and discuss potential extension to general manifolds by showing a construction on the torus

math.ST↗

arXiv2021

The Classical Multidimensional Scaling Revisited

We reexamine the the classical multidimensional scaling (MDS). We study some special cases, in particular, the exact solution for the sub-space formed by the 3 dimensional principal coordinates is derived. Also we give the extreme case when the points are collinear. Some insight into the effect on the MDS solution of the excluded eigenvalues (could be both positive as well as negative) of the doubly centered matrix is provided. As an illustration, we work through an example to understand the distortion in the MDS construction with positive and negative eigenvalues.

stat.ME↗

arXiv2021

Mixture models for spherical data with applications to protein bioinformatics

Finite mixture models are fitted to spherical data. Kent distributions are used for the components of the mixture because they allow considerable flexibility. Previous work on such mixtures has used an approximate maximum likelihood estimator for the parameters of a single component. However, the approximation causes problems when using the EM algorithm to estimate the parameters in a mixture model. Hence the exact maximum likelihood estimator is used here for the individual components. This paper is motivated by a challenging prize problem in structural bioinformatics of how proteins fold. It is known that hydrogen bonds play a key role in the folding of a protein. We explore this hydrogen bond geometry using a data set describing bonds between two amino acids in proteins. An appropriate coordinate system to represent the hydrogen bond geometry is proposed, with each bond represented as a point on a sphere. We fit mixtures of Kent distributions to different subsets of the hydrogen bond data to gain insight into how the secondary structure elements bond together, since the distribution of hydrogen bonds depends on which secondary structure elements are involved.

math.ST↗

arXiv2021

Clustering Schemes on the Torus with Application to RNA Clashes

Molecular structures of RNA molecules reconstructed from X-ray crystallography frequently contain errors. Motivated by this problem we examine clustering on a torus since RNA shapes can be described by dihedral angles. A previously developed clustering method for torus data involves two tuning parameters and we assess clustering results for different parameter values in relation to the problem of so-called RNA clashes. This clustering problem is part of the dynamically evolving field of statistics on manifolds. Statistical problems on the torus highlight general challenges for statistics on manifolds. Therefore, the torus PCA and clustering methods we propose make an important contribution to directional statistics and statistics on manifolds in general.

q-bio.BM↗

arXiv2020

Langevin diffusions on the torus: estimation and applications

We introduce stochastic models for continuous-time evolution of angles and develop their estimation. We focus on studying Langevin diffusions with stationary distributions equal to well-known distributions from directional statistics, since such diffusions can be regarded as toroidal analogues of the Ornstein-Uhlenbeck process. Their likelihood function is a product of transition densities with no analytical expression, but that can be calculated by solving the Fokker-Planck equation numerically through adequate schemes. We propose three approximate likelihoods that are computationally tractable: (i) a likelihood based on the stationary distribution; (ii) toroidal adaptations of the Euler and Shoji-Ozaki pseudo-likelihoods; (iii) a likelihood based on a specific approximation to the transition density of the wrapped normal process. A simulation study compares, in dimensions one and two, the approximate transition densities to the exact ones, and investigates the empirical performance of the approximate likelihoods. Finally, two diffusions are used to model the evolution of the backbone angles of the protein G (PDB identifier 1GB1) during a molecular dynamics simulation. The software package sdetorus implements the estimation methods and applications presented in the paper.

stat.ME↗

arXiv2020

A generative angular model of protein structure evolution

Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a generative, evolutionary model of protein structure and sequence that is valid on a local length scale. The model concerns the local dependencies between sequence and structure evolution in a pair of homologous proteins. The evolutionary trajectory between the two structures in the protein pair is treated as a random walk in dihedral angle space, which is modelled using a novel angular diffusion process on the two-dimensional torus. Coupling sequence and structure evolution in our model allows for modelling both "smooth" conformational changes and "catastrophic" conformational jumps, conditioned on the amino acid changes. The model has interpretable parameters and is comparatively more realistic than previous stochastic models, providing new insights into the relationship between sequence and structure evolution. For example, using the trained model we were able to identify an apparent sequence-structure evolutionary motif present in a large number of homologous protein pairs. The generative nature of our model enables us to evaluate its validity and its ability to simulate aspects of protein evolution conditioned on an amino acid sequence, a related amino acid sequence, a related structure or any combination thereof.

q-bio.PE↗

arXiv2020

Toroidal diffusions and protein structure evolution

This chapter shows how toroidal diffusions are convenient methodological tools for modelling protein evolution in a probabilistic framework. The chapter addresses the construction of ergodic diffusions with stationary distributions equal to well-known directional distributions, which can be regarded as toroidal analogues of the Ornstein-Uhlenbeck process. The important challenges that arise in the estimation of the diffusion parameters require the consideration of tractable approximate likelihoods and, among the several approaches introduced, the one yielding a specific approximation to the transition density of the wrapped normal process is shown to give the best empirical performance on average. This provides the methodological building block for Evolutionary Torus Dynamic Bayesian Network (ETDBN), a hidden Markov model for protein evolution that emits a wrapped normal process and two continuous-time Markov chains per hidden state. The chapter describes the main features of ETDBN, which allows for both "smooth" conformational changes and "catastrophic" conformational jumps, and several empirical benchmarks. The insights into the relationship between sequence and structure evolution that ETDBN provides are illustrated in a case study.

stat.ME↗

arXiv2015

Torus Principal Component Analysis with an Application to RNA Structures

There are several cutting edge applications needing PCA methods for data on tori and we propose a novel torus-PCA method with important properties that can be generally applied. There are two existing general methods: tangent space PCA and geodesic PCA. However, unlike tangent space PCA, our torus-PCA honors the cyclic topology of the data space whereas, unlike geodesic PCA, our torus-PCA produces a variety of non-winding, non-dense descriptors. This is achieved by deforming tori into spheres and then using a variant of the recently developed principle nested spheres analysis. This PCA analysis involves a step of small sphere fitting and we provide an improved test to avoid overfitting. However, deforming tori into spheres creates singularities. We introduce a data-adaptive pre-clustering technique to keep the singularities away from the data. For the frequently encountered case that the residual variance around the PCA main component is small, we use a post-mode hunting technique for more fine-grained clustering. Thus in general, there are three successive interrelated key steps of torus-PCA in practice: pre-clustering, deformation, and post-mode hunting. We illustrate our method with two recently studied RNA structure (tori) data sets: one is a small RNA data set which is established as the benchmark for PCA and we validate our method through this data. Another is a large RNA data set (containing the small RNA data set) for which we show that our method provides interpretable principal components as well as giving further insight into its structure.

stat.ME↗

arXiv2014

A Fast Algorithm for Sampling from the Posterior of a von Mises distribution

Motivated by molecular biology, there has been an upsurge of research activities in directional statistics in general and its Bayesian aspect in particular. The central distribution for the circular case is von Mises distribution which has two parameters (mean and concentration) akin to the univariate normal distribution. However, there has been a challenge to sample efficiently from the posterior distribution of the concentration parameter. We describe a novel, highly efficient algorithm to sample from the posterior distribution and fill this long-standing gap.

stat.CO↗