Bayesian Clustering Using Hidden Markov Random Fields in Spatial Population Genetics

By François, Olivier; Ancelet, Sophie et al. | Genetics, October 2006 | Go to article overview

Bayesian Clustering Using Hidden Markov Random Fields in Spatial Population Genetics


François, Olivier, Ancelet, Sophie, Guillot, Gilles, Genetics


ABSTRACT

We introduce a new Bayesian clustering algorithm for studying population structure using individually geo-referenced multilocus data sets. The algorithm is based on the concept of hidden Markov random field, which models the spatial dependencies at the cluster membership level. We argue that (i) a Markov chain Monte Carlo procedure can implement the algorithm efficiently, (ii) it can detect significant geographical discontinuities in allele frequencies and regulate the number of clusters, (iii) it can check whether the clusters obtained without the use of spatial priors are robust to the hypothesis of discontinuous geographical variation in allele frequencies, and (iv) it can reduce the number of loci required to obtain accurate assignments. We illustrate and discuss the implementation issues with the Scandinavian brown bear and the human CEPH diversity panel data set.

(ProQuest-CSA LLC: ... denotes formulae omitted.)

IT has been a recent matter of debate to decide whether clusters identified by Bayesian algorithms were artificially detected structures emerging from uneven sampling along clines or were actually welldifferentiated groups (SERRE and PÄÄBO 2004; ROSENBERG et al. 2005). It has indeed been suggested that uneven sampling during the experimental design might in- fluence clustering patterns and that the degree of clustering might be diminished by use of samples with greater spatial homogeneity. This dilemma has even introduced doubt about whether Bayesian clustering algorithms are appropriate tools for studying genetic structure in populations with continuous variation of allele frequencies.

Such issues have been reported after a study of genetic structure of human populations by ROSENBERG et al. (2002). Without the use of predefined populations, this study inferred the geographical ancestries of individuals from 52 worldwide samples with individuals genotyped at 377 microsatellite loci. Using the Bayesian clustering program STRUCTURE (PRITCHARD et al. 2000) and increasing the number of loci from 377 to 993, ROSENBERG et al. (2005) have shown that the six clusters found in their previous study are robust and, at the notable exception of the genetic isolate Kalash, that they match with the major geographic regions in the world. These clusters were interpreted as arising from small discontinuities in allele frequencies when geographical barriers are crossed.

In the latter and other applications of clustering algorithms, the spatial data are actually treated off line and are not part of the modeling. Bayesian models such as those developed by PRITCHARD et al. (2000), DAWSON and BELKHIR (2001), or CORANDER et al. (2003) nevertheless offer a natural and appropriate framework for including spatial prior information when assigning an individual to a fixed number of clusters. For example, a recent study by GUILLOT et al. (2005) used spatial explicit priors in a full-Bayes perspective and successfully identified genetic barriers in a wolverine population. An assignment method was also used by WASSER et al. (2004) to infer the spatial origin of African elephants. Here we argue that modified Bayesian algorithms can provide additional evidence to solve cline/ cluster dilemmas such as those discussed in ROSENBERG et al. (2005). A natural way to proceed is to include priors on continuous variation of genetic diversity in the Bayesian model used by STRUCTURE and check whether or not the previously discussed clusters are robust.

In this study, we present a new hierarchical Bayes algorithm that incorporates models for geographical continuity of allele frequencies. This is achieved by using hidden Markov random fields (HMRFs) as prior distributions on cluster membership. An informal defi- nition of HMRFs states that allele frequencies at a specific geographical site are more likely to be close to the allele frequencies at neighboring sites than at distant sites. The problem of local differentiation may also be studied in terms of change in correlation with distance as considered by MALÉCOT (1948), where "individuals living nearby tend to be more alike than those living far apart" (KIMURA and WEISS 1964, p. …

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