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Register a new userTopological Data Analysis of Single-cell Hi-C Contact Maps
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Added by
Mathieu Carri\\`ere
Publication date
2018
fields
Informatics Engineering
and research's language is
English
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In this article, we show how the recent statistical techniques developed in Topological Data Analysis for the Mapper algorithm can be extended and leveraged to formally define and statistically quantify the presence of topological structures coming from biological phenomena in datasets of CCC contact maps.
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Algorithms for persistent homology and zigzag persistent homology are well-studied for persistence modules where homomorphisms are induced by inclusion maps. In this paper, we propose a practical algorithm for computing persistence under $mathbb{Z}_2$ coefficients for a sequence of general simplicial maps and show how these maps arise naturally in some applications of topological data analysis. First, we observe that it is not hard to simulate simplicial maps by inclusion maps but not necessarily in a monotone direction. This, combined with the known algorithms for zigzag persistence, provides an algorithm for computing the persistence induced by simplicial maps. Our main result is that the above simple minded approach can be improved for a sequence of simplicial maps given in a monotone direction. A simplicial map can be decomposed into a set of elementary inclusions and vertex collapses--two atomic operations that can be supported efficiently with the notion of simplex annotations for computing persistent homology. A consistent annotation through these atomic operations implies the maintenance of a consistent cohomology basis, hence a homology basis by duality. While the idea of maintaining a cohomology basis through an inclusion is not new, maintaining them through a vertex collapse is new, which constitutes an important atomic operation for simulating simplicial maps. Annotations support the vertex collapse in addition to the usual inclusion quite naturally. Finally, we exhibit an application of this new tool in which we approximate the persistence diagram of a filtration of Rips complexes where vertex collapses are used to tame the blow-up in size.
The probability of two loci, separated by a certain genome length, being in contact can be inferred using the Chromosome Conformation Capture (3C) method and related Hi-C experiments. How to go from the contact map, a matrix listing the mean contact probabilities between a large number of pairs of loci, to an ensemble of three-dimensional structures is an open problem. A solution to this problem, without assuming an assumed energy function, would be the first step in understanding the way nature has solved the packaging of chromosomes in tight cellular spaces. We created a theory, based on polymer physics characteristics of chromosomes and the maximum entropy principles, referred to as HIPPS (Hi-C-Polymer-Physics-Structures) method, that allows us to calculate the 3D structures solely from Hi-C contact maps. We created an ensemble of 3D structures for the 23 chromosomes from lymphoblastoid cells using the measured contact maps as inputs. The HIPPS method shows that conformations of chromosomes are heterogeneous even in a single cell type. The differences in the conformational heterogeneity of the same chromosome in different cell types (normal as well as cancerous cells) can also be quantitatively discerned using our theory. We validate the method by showing that the calculated volumes of the 23 chromosomes from the predicted 3D structures are in good agreement with experimental estimates. Because the method is general, the 3D structures for any species may be calculated directly from the contact map without the need to assume a specific polymer model, as is customarily done.
We introduce a novel gradient descent algorithm extending the well-known Gradient Sampling methodology to the class of stratifiably smooth objective functions, which are defined as locally Lipschitz functions that are smooth on some regular pieces-called the strata-of the ambient Euclidean space. For this class of functions, our algorithm achieves a sub-linear convergence rate. We then apply our method to objective functions based on the (extended) persistent homology map computed over lower-star filters, which is a central tool of Topological Data Analysis. For this, we propose an efficient exploration of the corresponding stratification by using the Cayley graph of the permutation group. Finally, we provide benchmark and novel topological optimization problems, in order to demonstrate the utility and applicability of our framework.
Data analysis often concerns not only the space where data come from, but also various types of maps attached to data. In recent years, several related structures have been used to study maps on data, including Reeb spaces, mappers and multiscale mappers. The construction of these structures also relies on the so-called emph{nerve} of a cover of the domain. In this paper, we aim to analyze the topological information encoded in these structures in order to provide better understanding of these structures and facilitate their practical usage. More specifically, we show that the one-dimensional homology of the nerve complex $N(mathcal{U})$ of a path-connected cover $mathcal{U}$ of a domain $X$ cannot be richer than that of the domain $X$ itself. Intuitively, this result means that no new $H_1$-homology class can be created under a natural map from $X$ to the nerve complex $N(mathcal{U})$. Equipping $X$ with a pseudometric $d$, we further refine this result and characterize the classes of $H_1(X)$ that may survive in the nerve complex using the notion of emph{size} of the covering elements in $mathcal{U}$. These fundamental results about nerve complexes then lead to an analysis of the $H_1$-homology of Reeb spaces, mappers and multiscale mappers. The analysis of $H_1$-homology groups unfortunately does not extend to higher dimensions. Nevertheless, by using a map-induced metric, establishing a Gromov-Hausdorff convergence result between mappers and the domain, and interleaving relevant modules, we can still analyze the persistent homology groups of (multiscale) mappers to establish a connection to Reeb spaces.
The recent explosion of genomic data has underscored the need for interpretable and comprehensive analyses that can capture complex phylogenetic relationships within and across species. Recombination, reassortment and horizontal gene transfer constitute examples of pervasive biological phenomena that cannot be captured by tree-like representations. Starting from hundreds of genomes, we are interested in the reconstruction of potential evolutionary histories leading to the observed data. Ancestral recombination graphs represent potential histories that explicitly accommodate recombination and mutation events across orthologous genomes. However, they are computationally costly to reconstruct, usually being infeasible for more than few tens of genomes. Recently, Topological Data Analysis (TDA) methods have been proposed as robust and scalable methods that can capture the genetic scale and frequency of recombination. We build upon previous TDA developments for detecting and quantifying recombination, and present a novel framework that can be applied to hundreds of genomes and can be interpreted in terms of minimal histories of mutation and recombination events, quantifying the scales and identifying the genomic locations of recombinations. We implement this framework in a software package, called TARGet, and apply it to several examples, including small migration between different populations, human recombination, and horizontal evolution in finches inhabiting the Galapagos Islands.
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