Algorithms for Molecular Biology最新文献

The development of a privacy-preserving technology is important for accelerating genome data sharing. This study proposes an algorithm that securely searches a variable-length substring match between a query and a database sequence. Our concept hinges on a technique that efficiently applies FM-index for a secret-sharing scheme. More precisely, we developed an algorithm that can achieve a secure table lookup in such a way that [Formula: see text] is computed for a given depth of recursion where [Formula: see text] is an initial position, and V is a vector. We used the secure table lookup for vectors created based on FM-index. The notable feature of the secure table lookup is that time, communication, and round complexities are not dependent on the table length N, after the query input. Therefore, a substring match by reference to the FM-index-based table can also be conducted independently against the database length, and the entire search time is dramatically improved compared to previous approaches. We conducted an experiment using a human genome sequence with the length of 10 million as the database and a query with the length of 100 and found that the query response time of our protocol was at least three orders of magnitude faster than a non-indexed database search protocol under the realistic computation/network environment.

Background: There has been rapid development of probabilistic models and inference methods for transcript abundance estimation from RNA-seq data. These models aim to accurately estimate transcript-level abundances, to account for different biases in the measurement process, and even to assess uncertainty in resulting estimates that can be propagated to subsequent analyses. The assumed accuracy of the estimates inferred by such methods underpin gene expression based analysis routinely carried out in the lab. Although hyperparameter selection is known to affect the distributions of inferred abundances (e.g. producing smooth versus sparse estimates), strategies for performing model selection in experimental data have been addressed informally at best.

Results: We derive perplexity for evaluating abundance estimates on fragment sets directly. We adapt perplexity from the analogous metric used to evaluate language and topic models and extend the metric to carefully account for corner cases unique to RNA-seq. In experimental data, estimates with the best perplexity also best correlate with qPCR measurements. In simulated data, perplexity is well behaved and concordant with genome-wide measurements against ground truth and differential expression analysis. Furthermore, we demonstrate theoretically and experimentally that perplexity can be computed for arbitrary transcript abundance estimation models.

Conclusions: Alongside the derivation and implementation of perplexity for transcript abundance estimation, our study is the first to make possible model selection for transcript abundance estimation on experimental data in the absence of ground truth.

Motivation: k-mer counting is a common task in bioinformatic pipelines, with many dedicated tools available. Many of these tools produce in output k-mer count tables containing both k-mers and counts, easily reaching tens of GB. Furthermore, such tables do not support efficient random-access queries in general.

Results: In this work, we design an efficient representation of k-mer count tables supporting fast random-access queries. We propose to apply Compressed Static Functions (CSFs), with space proportional to the empirical zero-order entropy of the counts. For very skewed distributions, like those of k-mer counts in whole genomes, the only currently available implementation of CSFs does not provide a compact enough representation. By adding a Bloom filter to a CSF we obtain a Bloom-enhanced CSF (BCSF) effectively overcoming this limitation. Furthermore, by combining BCSFs with minimizer-based bucketing of k-mers, we build even smaller representations breaking the empirical entropy lower bound, for large enough k. We also extend these representations to the approximate case, gaining additional space. We experimentally validate these techniques on k-mer count tables of whole genomes (E. Coli and C. Elegans) and unassembled reads, as well as on k-mer document frequency tables for 29 E. Coli genomes. In the case of exact counts, our representation takes about a half of the space of the empirical entropy, for large enough k's.

Background: Cophylogeny reconciliation is a powerful method for analyzing host-parasite (or host-symbiont) co-evolution. It models co-evolution as an optimization problem where the set of all optimal solutions may represent different biological scenarios which thus need to be analyzed separately. Despite the significant research done in the area, few approaches have addressed the problem of helping the biologist deal with the often huge space of optimal solutions.

Results: In this paper, we propose a new approach to tackle this problem. We introduce three different criteria under which two solutions may be considered biologically equivalent, and then we propose polynomial-delay algorithms that enumerate only one representative per equivalence class (without listing all the solutions).

Conclusions: Our results are of both theoretical and practical importance. Indeed, as shown by the experiments, we are able to significantly reduce the space of optimal solutions while still maintaining important biological information about the whole space.

Background: SORTING BY TRANSPOSITIONS (SBT) is a classical problem in genome rearrangements. In 2012, SBT was proven to be [Formula: see text]-hard and the best approximation algorithm with a 1.375 ratio was proposed in 2006 by Elias and Hartman (EH algorithm). Their algorithm employs simplification, a technique used to transform an input permutation [Formula: see text] into a simple permutation [Formula: see text], presumably easier to handle with. The permutation [Formula: see text] is obtained by inserting new symbols into [Formula: see text] in a way that the lower bound of the transposition distance of [Formula: see text] is kept on [Formula: see text]. The simplification is guaranteed to keep the lower bound, not the transposition distance. A sequence of operations sorting [Formula: see text] can be mimicked to sort [Formula: see text].

Results and conclusions: First, using an algebraic approach, we propose a new upper bound for the transposition distance, which holds for all [Formula: see text]. Next, motivated by a problem identified in the EH algorithm, which causes it, in scenarios involving how the input permutation is simplified, to require one extra transposition above the 1.375-approximation ratio, we propose a new approximation algorithm to solve SBT ensuring the 1.375-approximation ratio for all [Formula: see text]. We implemented our algorithm and EH's. Regarding the implementation of the EH algorithm, two other issues were identified and needed to be fixed. We tested both algorithms against all permutations of size n, [Formula: see text]. The results show that the EH algorithm exceeds the approximation ratio of 1.375 for permutations with a size greater than 7. The percentage of computed distances that are equal to transposition distance, computed by the implemented algorithms are also compared with others available in the literature. Finally, we investigate the performance of both implementations on longer permutations of maximum length 500. From the experiments, we conclude that maximum and the average distances computed by our algorithm are a little better than the ones computed by the EH algorithm and the running times of both algorithms are similar, despite the time complexity of our algorithm being higher.

Background: Pattern matching is a key step in a variety of biological sequence analysis pipelines. The FM-index is a compressed data structure for pattern matching, with search run time that is independent of the length of the database text. Implementation of the FM-index is reasonably complicated, so that increased adoption will be aided by the availability of a fast and flexible FM-index library.

Results: We present AvxWindowedFMindex (AWFM-index), a lightweight, open-source, thread-parallel FM-index library written in C that is optimized for indexing nucleotide and amino acid sequences. AWFM-index introduces a new approach to storing FM-index data in a strided bit-vector format that enables extremely efficient computation of the FM-index occurrence function via AVX2 bitwise instructions, and combines this with optional on-disk storage of the index's suffix array and a cache-efficient lookup table for partial k-mer searches. The AWFM-index performs exact match count and locate queries faster than SeqAn3's FM-index implementation across a range of comparable memory footprints. When optimized for speed, AWFM-index is [Formula: see text]2-4x faster than SeqAn3 for nucleotide search, and [Formula: see text]2-6x faster for amino acid search; it is also [Formula: see text]4x faster with similar memory footprint when storing the suffix array in on-disk SSD storage.

Conclusions: AWFM-index is easy to incorporate into bioinformatics software, offers run-time performance parameterization, and provides clients with FM-index functionality at both a high-level (count or locate all instances of a query string) and low-level (step-wise control of the FM-index backward-search process). The open-source library is available for download at https://github.com/TravisWheelerLab/AvxWindowFmIndex.

Background: In the comparative genomics field, one of the goals is to estimate a sequence of genetic changes capable of transforming a genome into another. Genome rearrangement events are mutations that can alter the genetic content or the arrangement of elements from the genome. Reversal and transposition are two of the most studied genome rearrangement events. A reversal inverts a segment of a genome while a transposition swaps two consecutive segments. Initial studies in the area considered only the order of the genes. Recent works have incorporated other genetic information in the model. In particular, the information regarding the size of intergenic regions, which are structures between each pair of genes and in the extremities of a linear genome.

Results and conclusions: In this work, we investigate the SORTING BY INTERGENIC REVERSALS AND TRANSPOSITIONS problem on genomes sharing the same set of genes, considering the cases where the orientation of genes is known and unknown. Besides, we explored a variant of the problem, which generalizes the transposition event. As a result, we present an approximation algorithm that guarantees an approximation factor of 4 for both cases considering the reversal and transposition (classic definition) events, an improvement from the 4.5-approximation previously known for the scenario where the orientation of the genes is unknown. We also present a 3-approximation algorithm by incorporating the generalized transposition event, and we propose a greedy strategy to improve the performance of the algorithms. We performed practical tests adopting simulated data which indicated that the algorithms, in both cases, tend to perform better when compared with the best-known algorithms for the problem. Lastly, we conducted experiments using real genomes to demonstrate the applicability of the algorithms.