SearcharxivSearch

arXiv subjects

Yann Ponty

Publications and source records attributed to Yann Ponty.

At least 19 recordsLinked to original sources

Sequence graphs realizations and ambiguity in language models

Several popular language models represent local contexts in an input text $x$ as bags of words. Such representations are naturally encoded by a sequence graph whose vertices are the distinct words occurring in $x$, with edges representing the (ordered) co-occurrence of two words within a sliding window of size $w$. However, this compressed representation is not generally bijective: some may be ambiguous, admitting several realizations as a sequence, while others may not admit any realization. In this paper, we study the realizability and ambiguity of sequence graphs from a combinatorial and algorithmic point of view. We consider the existence and enumeration of realizations of a sequence graph under multiple settings: window size $w$, presence/absence of graph orientation, and presence/absence of weights (multiplicities). When $w=2$, we provide polynomial time algorithms for realizability and enumeration in all cases except the undirected/weighted setting, where we show the $\#$P-hardness of enumeration. For $w \ge 3$, we prove the hardness of all variants, even when $w$ is considered as a constant, with the notable exception of the undirected unweighted case for which we propose XP algorithms for both problems, tight due to a corresponding $W[1]-$hardness result. We conclude with an integer program formulation to solve the realizability problem, and a dynamic programming algorithm to solve the enumeration problem in instances of moderate sizes. This work leaves open the membership to NP of both problems, a non-trivial question due to the existence of minimum realizations having size exponential on the instance encoding.

cs.DS

Effective Rotation-invariant Point CNN with Spherical Harmonics kernels

We present a novel rotation invariant architecture operating directly on point cloud data. We demonstrate how rotation invariance can be injected into a recently proposed point-based PCNN architecture, at all layers of the network, achieving invariance to both global shape transformations, and to local rotations on the level of patches or parts, useful when dealing with non-rigid objects. We achieve this by employing a spherical harmonics based kernel at different layers of the network, which is guaranteed to be invariant to rigid motions. We also introduce a more efficient pooling operation for PCNN using space-partitioning data-structures. This results in a flexible, simple and efficient architecture that achieves accurate results on challenging shape analysis tasks including classification and segmentation, without requiring data-augmentation, typically employed by non-invariant approaches.

cs.CV

Counting and sampling gene family evolutionary histories in the duplication-loss and duplication-loss-transfer models

Given a set of species whose evolution is represented by a species tree, a gene family is a group of genes having evolved from a single ancestral gene. A gene family evolves along the branches of a species tree through various mechanisms, including - but not limited to - speciation, gene duplication, gene loss, horizontal gene transfer. The reconstruction of a gene tree representing the evolution of a gene family constrained by a species tree is an important problem in phylogenomics. However, unlike in the multispecies coalescent evolutionary model, very little is known about the search space for gene family histories accounting for gene duplication, gene loss and horizontal gene transfer (the DLT-model). We introduce the notion of evolutionary histories defined as a binary ordered rooted tree describing the evolution of a gene family, constrained by a species tree in the DLT-model. We provide formal grammars describing the set of all evolutionary histories that are compatible with a given species tree, whether it is ranked or unranked. These grammars allow us, using either analytic combinatorics or dynamic programming, to efficiently compute the number of histories of a given size, and also to generate random histories of a given size under the uniform distribution. We apply these tools to obtain exact asymptotics for the number of gene family histories for two species trees, the rooted caterpillar and the complete binary tree, as well as estimates of the range of the exponential growth factor of the number of histories for random species trees of size up to 25. Our results show that including horizontal gene transfer induce a dramatic increase of the number of evolutionary histories. We also show that, within ranked species trees, the number of evolutionary histories in the DLT-model is almost independent of the species tree topology.

math.CO

Small-world networks and RNA secondary structures

Let Sn denote the network of all RNA secondary structures of length n, in which undirected edges exist between structures s, t such that t is obtained from s by the addition, removal or shift of a single base pair. Using context-free grammars, generating functions and complex analysis, we show that the asymptotic average degree is O(n) and that the asymptotic clustering coeffcient is O(1/n), from which it follows that the family Sn, n = 1,2,3,... of secondary structure networks is not small-world.

q-bio.BM

Fixed-Parameter Tractable Sampling for RNA Design with Multiple Target Structures

The design of multi-stable RNA molecules has important applications in biology, medicine, and biotechnology. Synthetic design approaches profit strongly from effective in-silico methods, which can tremendously impact their cost and feasibility. We revisit a central ingredient of most in-silico design methods: the sampling of sequences for the design of multi-target structures, possibly including pseudoknots. For this task, we present the efficient, tree decomposition-based algorithm. Our fixed parameter tractable approach is underpinned by establishing the P-hardness of uniform sampling. Modeling the problem as a constraint network, our program supports generic Boltzmann-weighted sampling for arbitrary additive RNA energy models; this enables the generation of RNA sequences meeting specific goals like expected free energies or \GCb-content. Finally, we empirically study general properties of the approach and generate biologically relevant multi-target Boltzmann-weighted designs for a common design benchmark. Generating seed sequences with our program, we demonstrate significant improvements over the previously best multi-target sampling strategy (uniform sampling).Our software is freely available at: https://github.com/yannponty/RNARedPrint .

q-bio.QM

Combinatorial RNA Design Designability and Structure-Approximating Algorithm in Watson-Crick and Nussinov-Jacobson Energy Models

We consider the Combinatorial RNA Design problem, a minimal instance of RNA design where one must produce an RNA sequence that adopts a given secondary structure as its minimal free-energy structure. We consider two free-energy models where the contributions of base pairs are additive and independent: the purely combinatorial Watson-Crick model, which only allows equally-contributing A -- U and C -- G base pairs, and the real-valued Nussinov-Jacobson model, which associates arbitrary energies to A -- U, C -- G and G -- U base pairs. We first provide a complete characterization of designable structures using restricted alphabets and, in the four-letter alphabet, provide a complete characterization for designable structures without unpaired bases. When unpaired bases are allowed, we characterize extensive classes of (non-)designable structures, and prove the closure of the set of designable structures under the stutter operation. Membership of a given structure to any of the classes can be tested in $Θ$(n) time, including the generation of a solution sequence for positive instances. Finally, we consider a structure-approximating relaxation of the design, and provide a $Θ$(n) algorithm which, given a structure S that avoids two trivially non-designable motifs, transforms S into a designable structure constructively by adding at most one base-pair to each of its stems.

q-bio.QM

Counting, generating and sampling tree alignments

Pairwise ordered tree alignment are combinatorial objects that appear in RNA secondary structure comparison. However, the usual representation of tree alignments as supertrees is ambiguous, i.e. two distinct supertrees may induce identical sets of matches between identical pairs of trees. This ambiguity is uninformative, and detrimental to any probabilistic analysis.In this work, we consider tree alignments up to equivalence. Our first result is a precise asymptotic enumeration of tree alignments, obtained from a context-free grammar by mean of basic analytic combinatorics. Our second result focuses on alignments between two given ordered trees $S$ and $T$. By refining our grammar to align specific trees, we obtain a decomposition scheme for the space of alignments, and use it to design an efficient dynamic programming algorithm for sampling alignments under the Gibbs-Boltzmann probability distribution. This generalizes existing tree alignment algorithms, and opens the door for a probabilistic analysis of the space of suboptimal RNA secondary structures alignments.

q-bio.QM

Combinatorial RNA Design: Designability and Structure-Approximating Algorithm

In this work, we consider the Combinatorial RNA Design problem, a minimal instance of the RNA design problem which aims at finding a sequence that admits a given target as its unique base pair maximizing structure. We provide complete characterizations for the structures that can be designed using restricted alphabets. Under a classic four-letter alphabet, we provide a complete characterization of designable structures without unpaired bases. When unpaired bases are allowed, we provide partial characterizations for classes of designable/undesignable structures, and show that the class of designable structures is closed under the stutter operation. Membership of a given structure to any of the classes can be tested in linear time and, for positive instances, a solution can be found in linear time. Finally, we consider a structure-approximating version of the problem that allows to extend bands (helices) and, assuming that the input structure avoids two motifs, we provide a linear-time algorithm that produces a designable structure with at most twice more base pairs than the input structure.

q-bio.QM

Assessing the robustness of parsimonious predictions for gene neighborhoods from reconciled phylogenies

The availability of a large number of assembled genomes opens the way to study the evolution of syntenic character within a phylogenetic context. The DeCo algorithm, recently introduced by B{é}rard et al. allows the computation of parsimonious evolutionary scenarios for gene adjacencies, from pairs of reconciled gene trees. Following the approach pioneered by Sturmfels and Pachter, we describe how to modify the DeCo dynamic programming algorithm to identify classes of cost schemes that generates similar parsimonious evolutionary scenarios for gene adjacencies, as well as the robustness to changes to the cost scheme of evolutionary events of the presence or absence of specific ancestral gene adjacencies. We apply our method to six thousands mammalian gene families, and show that computing the robustness to changes to cost schemes provides new and interesting insights on the evolution of gene adjacencies and the DeCo model.

q-bio.QM

Flexible RNA design under structure and sequence constraints using formal languages

The problem of RNA secondary structure design (also called inverse folding) is the following: given a target secondary structure, one aims to create a sequence that folds into, or is compatible with, a given structure. In several practical applications in biology, additional constraints must be taken into account, such as the presence/absence of regulatory motifs, either at a specific location or anywhere in the sequence. In this study, we investigate the design of RNA sequences from their targeted secondary structure, given these additional sequence constraints. To this purpose, we develop a general framework based on concepts of language theory, namely context-free grammars and finite automata. We efficiently combine a comprehensive set of constraints into a unifying context-free grammar of moderate size. From there, we use generic generic algorithms to perform a (weighted) random generation, or an exhaustive enumeration, of candidate sequences. The resulting method, whose complexity scales linearly with the length of the RNA, was implemented as a standalone program. The resulting software was embedded into a publicly available dedicated web server. The applicability demonstrated of the method on a concrete case study dedicated to Exon Splicing Enhancers, in which our approach was successfully used in the design of \emph{in vitro} experiments.

q-bio.QM

Using structural and evolutionary information to detect and correct pyrosequencing errors in non-coding RNAs

Analysis of the sequence-structure relationship in RNA molecules are essential to evolutionary studies but also to concrete applications such as error-correction methodologies in sequencing technologies. The prohibitive sizes of the mutational and conformational landscapes combined with the volume of data to proceed require efficient algorithms to compute sequence-structure properties. More specifically, here we aim to calculate which mutations increase the most the likelihood of a sequence to a given structure and RNA family. In this paper, we introduce RNApyro, an efficient linear-time and space inside-outside algorithm that computes exact mutational probabilities under secondary structure and evolutionary constraints given as a multiple sequence alignment with a consensus structure. We develop a scoring scheme combining classical stacking base pair energies to novel isostericity scales, and apply our techniques to correct point-wise errors in 5s and 16s rRNA sequences. Our results suggest that RNApyro is a promising algorithm to complement existing tools in the NGS error-correction pipeline.

q-bio.QM

Non-redundant random generation algorithms for weighted context-free languages

We address the non-redundant random generation of $k$ words of length $n$ in a context-free language. Additionally, we want to avoid a predefined set of words. We study a rejection-based approach, whose worst-case time complexity is shown to grow exponentially with $k$ for some specifications and in the limit case of a coupon collector. We propose two algorithms respectively based on the recursive method and on an unranking approach. We show how careful implementations of these algorithms allow for a non-redundant generation of $k$ words of length $n$ in $\mathcal{O}(k\cdot n\cdot \log{n})$ arithmetic operations, after a precomputation of $Θ(n)$ numbers. The overall complexity is therefore dominated by the generation of $k$ words, and the non-redundancy comes at a negligible cost.

cs.FL

Tree decomposition and parameterized algorithms for RNA structure-sequence alignment including tertiary interactions and pseudoknots

We present a general setting for structure-sequence comparison in a large class of RNA structures that unifies and generalizes a number of recent works on specific families on structures. Our approach is based on tree decomposition of structures and gives rises to a general parameterized algorithm, where the exponential part of the complexity depends on the family of structures. For each of the previously studied families, our algorithm has the same complexity as the specific algorithm that had been given before.

q-bio.QM

Rule-weighted and terminal-weighted context-free grammars have identical expressivity

Two formalisms, both based on context-free grammars, have recently been proposed as a basis for a non-uniform random generation of combinatorial objects. The former, introduced by Denise et al, associates weights with letters, while the latter, recently explored by Weinberg et al in the context of random generation, associates weights to transitions. In this short note, we use a simple modification of the Greibach Normal Form transformation algorithm, due to Blum and Koch, to show the equivalent expressivities, in term of their induced distributions, of these two formalisms.

cs.CL

The weighted words collector

Motivated by applications in bioinformatics, we consider the word collector problem, i.e. the expected number of calls to a random weighted generator of words of length $n$ before the full collection is obtained. The originality of this instance of the non-uniform coupon collector lies in the, potentially large, multiplicity of the words/coupons of a given probability/composition. We obtain a general theorem that gives an asymptotic equivalent for the expected waiting time of a general version of the Coupon Collector. This theorem is especially well-suited for classes of coupons featuring high multiplicities. Its application to a given language essentially necessitates some knowledge on the number of words of a given composition/probability. We illustrate the application of our theorem, in a step-by-step fashion, on three exemplary languages, revealing asymptotic regimes in $Θ(μ(n)\cdot n)$ and $Θ(μ(n)\cdot \log n)$, where $μ(n)$ is the sum of weights over words of length $n$.

cs.DM

A Combinatorial Framework for Designing (Pseudoknotted) RNA Algorithms

We extend an hypergraph representation, introduced by Finkelstein and Roytberg, to unify dynamic programming algorithms in the context of RNA folding with pseudoknots. Classic applications of RNA dynamic programming energy minimization, partition function, base-pair probabilities...) are reformulated within this framework, giving rise to very simple algorithms. This reformulation allows one to conceptually detach the conformation space/energy model -- captured by the hypergraph model -- from the specific application, assuming unambiguity of the decomposition. To ensure the latter property, we propose a new combinatorial methodology based on generating functions. We extend the set of generic applications by proposing an exact algorithm for extracting generalized moments in weighted distribution, generalizing a prior contribution by Miklos and al. Finally, we illustrate our full-fledged programme on three exemplary conformation spaces (secondary structures, Akutsu's simple type pseudoknots and kissing hairpins). This readily gives sets of algorithms that are either novel or have complexity comparable to classic implementations for minimization and Boltzmann ensemble applications of dynamic programming.

q-bio.QM

Non-redundant random generation from weighted context-free languages

We address the non-redundant random generation of k words of length n from a context-free language. Additionally, we want to avoid a predefined set of words. We study the limits of a rejection-based approach, whose time complexity is shown to grow exponentially in k in some cases. We propose an alternative recursive algorithm, whose careful implementation allows for a non-redundant generation of k words of size n in O(kn log n) arithmetic operations after the precomputation of O(n) numbers. The overall complexity is therefore dominated by the generation of k words, and the non-redundancy comes at a negligible cost.

cs.DS