Genome graphs can represent genetic variation and sequence uncertainty. Aligning sequences to genome graphs is key to many applications, including error correction, genome assembly, and genotyping of variants in a pangenome graph. Yet, so far, this step is often prohibitively slow. We present GraphAligner, a tool for aligning long reads to genome graphs. Compared to the state-of-the-art tools, GraphAligner is 13x faster and uses 3x less memory. When employing GraphAligner for error correction, we find it to be more than twice as accurate and over 12x faster than extant tools.Availability: Package manager: 
https://anaconda.org/bioconda/graphaligner

and source code: 
https://github.com/maickrau/GraphAligner

/pdf/graphaligner-rapid-and-versatile-sequence-to-graph-alignment-1f35izxmro.pdf

GraphAligner: rapid and versatile sequence-to-graph alignment.

Exact string matching in labeled graphs is the problem of searching paths of a graph G=(V,E) such that the concatenation of their node labels is equal to the given pattern string P[1..m]. This basic problem can be found at the heart of more complex operations on variation graphs in computational biology, of query operations in graph databases, and of analysis operations in heterogeneous networks.
We prove a conditional lower bound stating that, for any constant epsilon>0, an O(|E|^{1 - epsilon} m)-time, or an O(|E| m^{1 - epsilon})-time algorithm for exact string matching in graphs, with node labels and patterns drawn from a binary alphabet, cannot be achieved unless the Strong Exponential Time Hypothesis (SETH) is false. This holds even if restricted to undirected graphs with maximum node degree two, i.e. to zig-zag matching in bidirectional strings, or to deterministic directed acyclic graphs whose nodes have maximum sum of indegree and outdegree three. These restricted cases make the lower bound stricter than what can be directly derived from related bounds on regular expression matching (Backurs and Indyk, FOCS'16). In fact, our bounds are tight in the sense that lowering the degree or the alphabet size yields linear-time solvable problems. 
An interesting corollary is that exact and approximate matching are equally hard (quadratic time) in graphs under SETH. In comparison, the same problems restricted to strings have linear-time vs quadratic-time solutions, respectively (approximate pattern matching having also a matching SETH lower bound (Backurs and Indyk, STOC'15)).

https://drops.dagstuhl.de/opus/volltexte/2019/10631/pdf/LIPIcs-ICALP-2019-55.pdf/

On the Complexity of String Matching for Graphs

Exact string matching in labeled graphs is the problem of searching paths of a graph G=(V, E) such that the concatenation of their node labels is equal to a given pattern string P[1.m]. This basic problem can be found at the heart of more complex operations on variation graphs in computational biology, of query operations in graph databases, and of analysis operations in heterogeneous networks. We prove a conditional lower bound stating that, for any constant ε > 0, an O(|E|1 - ε m) time, or an O(|E| m1 - ε)time algorithm for exact string matching in graphs, with node labels and pattern drawn from a binary alphabet, cannot be achieved unless the Strong Exponential Time Hypothesis (SETH) is false. This holds even if restricted to undirected graphs with maximum node degree 2—that is, to zig-zag matching in bidirectional strings, or to deterministic directed acyclic graphs whose nodes have maximum sum of indegree and outdegree 3. These restricted cases make the lower bound stricter than what can be directly derived from related bounds on regular expression matching (Backurs and Indyk, FOCS’16). In fact, our bounds are tight in the sense that lowering the degree or the alphabet size yields linear time solvable problems. An interesting corollary is that exact and approximate matching are equally hard (i.e., quadratic time) in graphs under SETH. In comparison, the same problems restricted to strings have linear time vs quadratic time solutions, respectively (approximate pattern matching having also a matching SETH lower bound (Backurs and Indyk, STOC’15)).

/pdf/on-the-complexity-of-string-matching-for-graphs-2jywlbhx.pdf

Computational pangenomics is an emerging research field that is changing the way computer scientists are facing challenges in biological sequence analysis. In past decades, contributions from combinatorics, stringology, graph theory and data structures were essential in the development of a plethora of software tools for the analysis of the human genome. These tools allowed computational biologists to approach ambitious projects at population scale, such as the 1000 Genomes Project. A major contribution of the 1000 Genomes Project is the characterization of a broad spectrum of genetic variations in the human genome, including the discovery of novel variations in the South Asian, African and European populations-thus enhancing the catalogue of variability within the reference genome. Currently, the need to take into account the high variability in population genomes as well as the specificity of an individual genome in a personalized approach to medicine is rapidly pushing the abandonment of the traditional paradigm of using a single reference genome. A graph-based representation of multiple genomes, or a graph pangenome, is replacing the linear reference genome. This means completely rethinking well-established procedures to analyze, store, and access information from genome representations. Properly addressing these challenges is crucial to face the computational tasks of ambitious healthcare projects aiming to characterize human diversity by sequencing 1M individuals (Stark et al. 2019). This tutorial aims to introduce readers to the most recent advances in the theory of data structures for the representation of graph pangenomes. We discuss efficient representations of haplotypes and the variability of genotypes in graph pangenomes, and highlight applications in solving computational problems in human and microbial (viral) pangenomes. 

/pdf/computational-graph-pangenomics-a-tutorial-on-data-2juhnhk8.pdf

Computational graph pangenomics: a tutorial on data structures and their applications

Indexing strings via prefix (or suffix) sorting is, arguably, one of the most successful algorithmic techniques developed in the last decades. Can indexing be extended to languages? The main contribution of this paper is to initiate the study of the sub-class of regular languages accepted by an automaton whose states can be prefix-sorted. Starting from the recent notion of Wheeler graph [Gagie et al., TCS 2017]---which extends naturally the concept of prefix sorting to labeled graphs---we investigate the properties of Wheeler languages, that is, regular languages admitting an accepting Wheeler finite automaton. We first characterize this family as the natural extension of regular languages endowed with the co-lexicographic ordering: the sorted prefixes of strings belonging to a Wheeler language are partitioned into a finite number of co-lexicographic intervals, each formed by elements from a single Myhill-Nerode equivalence class. We proceed by proving several results related to Wheeler automata: (i) We show that every Wheeler NFA (WNFA) with n states admits an equivalent Wheeler DFA (WDFA) with at most 2n − 1 − |Σ| states (Σ being the alphabet) that can be computed in O(n3) time. (ii) We describe a quadratic algorithm to prefix-sort a proper superset of the WDFAs, a O(n log n)-time online algorithm to sort acyclic WDFAs, and an optimal linear-time offline algorithm to sort general WDFAs. (iii) We provide a minimization theorem that characterizes the smallest WDFA recognizing the same language of any input WDFA. The corresponding constructive algorithm runs in optimal linear time in the acyclic case, and in O(n log n) time in the general case. (iv) We show how to compute the smallest WDFA equivalent to any acyclic DFA in nearly-optimal time. Our contributions imply new results of independent interest. Contributions (i-iii) provide a new class of NFAs for which the minimization problem can be approximated within a constant factor in polynomial time. Contribution (iv) provides a provably minimum-size solution for the well-studied problem of indexing deterministic-acyclic graphs for linear-time pattern matching queries.

Regular languages meet prefix sorting

We consider the following string matching problem on a node-labeled graph $G=(V,E)$: given a pattern string $P$, decide whether there exists a path in $G$ whose concatenation of node labels equals $P$. This is a basic primitive in various problems in bioinformatics, graph databases, or networks. The hardness results of Backurs and Indyk (FOCS 2016) imply that this problem cannot be solved in better than $O(|E||P|)$ time, under the Orthogonal Vectors Hypothesis (OVH), and this holds even under various restrictions on the graph (Equi et al., ICALP 2019). 
In this paper we consider its offline version, namely the one in which we are allowed to index the graph in order to support time-efficient string matching queries. Indeed, it was tantalizing in the string matching community to believe that sub-quadratic time queries can be achieved, e.g. at the cost of a high-degree polynomial-time indexing. 
We disprove this belief, showing that, under OVH, no polynomial-time index can support querying $P$ in time $O(|E|^\delta|P|^\beta)$, with either $\delta < 1$ or $\beta < 1$. We prove this tight bound employing a known self-reducibility technique, e.g. from the field of dynamic algorithms, which translates conditional lower bounds for an online problem to its offline version. 
As a side-contribution, we formalize this technique with the notion of linear independent-components reduction, allowing for a simple proof of our result. As another illustration of our technique, we also translate the quadratic conditional lower bound of Backurs and Indyk (STOC 2015) for the problem of matching a query string inside a text, under edit distance. We obtain an analogous tight quadratic lower bound for its offline version, improving the recent result of Cohen-Addad, Feuilloley and Starikovskaya (SODA 2019), but with a slightly different boundary condition.

pdf/graphs-cannot-be-indexed-in-polynomial-time-for-sub-1w1dx4bo51.pdf

Graphs cannot be indexed in polynomial time for sub-quadratic time string matching, unless SETH fails

The string matching problem on a node-labeled graph $G=(V,E)$ asks whether a given pattern string P has an occurrence in G, in the form of a path whose concatenation of node labels equals P This is a basic primitive in various problems in bioinformatics, graph databases, or networks, but only recently proven to have a O(|E||P|)-time lower bound, under the Orthogonal Vectors Hypothesis (OVH) We consider here its indexed version, in which we can index the graph in order to support time-efficient string queries

Graphs Cannot Be Indexed in Polynomial Time for Sub-quadratic Time String Matching, Unless SETH Fails.

We introduce a compact pangenome representation based on an optimal segmentation concept that aims to reconstruct founder sequences from a multiple sequence alignment (MSA). Such founder sequences have the feature that each row of the MSA is a recombination of the founders. Several linear time dynamic programming algorithms have been previously devised to optimize segmentations that induce founder blocks that then can be concatenated into a set of founder sequences. All possible concatenation orders can be expressed as a founder block graph. We observe a key property of such graphs: if the node labels (founder segments) do not repeat in the paths of the graph, such graphs can be indexed for efficient string matching. We call such graphs segment repeat-free founder block graphs. 
We give a linear time algorithm to construct a segment repeat-free founder block graph given an MSA. The algorithm combines techniques from the founder segmentation algorithms (Cazaux et al. SPIRE 2019) and fully-functional bidirectional Burrows-Wheeler index (Belazzougui and Cunial, CPM 2019). We derive a succinct index structure to support queries of arbitrary length in the paths of the graph. 
Experiments on an MSA of SAR-CoV-2 strains are reported. An MSA of size $410\times 29811$ is compacted in one minute into a segment repeat-free founder block graph of 3900 nodes and 4440 edges. The maximum length and total length of node labels is 12 and 34968, respectively. The index on the graph takes only $3\%$ of the size of the MSA.

Linear Time Construction of Indexable Founder Block Graphs.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Massimo Equi

Author Tools

Chat about Author

Papers

On the Complexity of String Matching for Graphs

On the Complexity of String Matching for Graphs

Graphs cannot be indexed in polynomial time for sub-quadratic time string matching, unless SETH fails

Graphs Cannot Be Indexed in Polynomial Time for Sub-quadratic Time String Matching, Unless SETH Fails.

Linear Time Construction of Indexable Founder Block Graphs.