{"title":"Semi-nonparametric modeling of topological domain formation from epigenetic data.","authors":"Emre Sefer, Carl Kingsford","doi":"10.1186/s13015-019-0142-y","DOIUrl":"https://doi.org/10.1186/s13015-019-0142-y","url":null,"abstract":"<p><strong>Background: </strong>Hi-C experiments capturing the 3D genome architecture have led to the discovery of topologically-associated domains (TADs) that form an important part of the 3D genome organization and appear to play a role in gene regulation and other functions. Several histone modifications have been independently associated with TAD formation, but their combinatorial effects on domain formation remain poorly understood at a global scale.</p><p><strong>Results: </strong>We propose a convex semi-nonparametric approach called <i>nTDP</i> based on Bernstein polynomials to explore the joint effects of histone markers on TAD formation as well as predict TADs solely from the histone data. We find a small subset of modifications to be predictive of TADs across species. By inferring TADs using our trained model, we are able to predict TADs across different species and cell types, without the use of Hi-C data, suggesting their effect is conserved. This work provides the first comprehensive joint model of the effect of histone markers on domain formation.</p><p><strong>Conclusions: </strong>Our approach, <i>nTDP</i>, can form the basis of a unified, explanatory model of the relationship between epigenetic marks and topological domain structures. It can be used to predict domain boundaries for cell types, species, and conditions for which no Hi-C data is available. The model may also be of use for improving Hi-C-based domain finders.</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":" ","pages":"4"},"PeriodicalIF":1.0,"publicationDate":"2019-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-019-0142-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37052618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SNPs detection by eBWT positional clustering.","authors":"Nicola Prezza, Nadia Pisanti, Marinella Sciortino, Giovanna Rosone","doi":"10.1186/s13015-019-0137-8","DOIUrl":"https://doi.org/10.1186/s13015-019-0137-8","url":null,"abstract":"<p><strong>Background: </strong>Sequencing technologies keep on turning cheaper and faster, thus putting a growing pressure for data structures designed to efficiently store raw data, and possibly perform analysis therein. In this view, there is a growing interest in alignment-free and reference-free variants calling methods that only make use of (suitably indexed) raw reads data.</p><p><strong>Results: </strong>We develop the <i>positional clustering</i> theory that (i) describes how the extended Burrows-Wheeler Transform (eBWT) of a collection of reads tends to cluster together bases that cover the same genome position (ii) predicts the size of such clusters, and (iii) exhibits an elegant and precise LCP array based procedure to locate such clusters in the eBWT. Based on this theory, we designed and implemented an alignment-free and reference-free SNPs calling method, and we devised a consequent SNPs calling pipeline. Experiments on both synthetic and real data show that SNPs can be detected with a simple scan of the eBWT and LCP arrays as, in accordance with our theoretical framework, they are within clusters in the eBWT of the reads. Finally, our tool intrinsically performs a reference-free evaluation of its accuracy by returning the coverage of each SNP.</p><p><strong>Conclusions: </strong>Based on the results of the experiments on synthetic and real data, we conclude that the positional clustering framework can be effectively used for the problem of identifying SNPs, and it appears to be a promising approach for calling other type of variants directly on raw sequencing data.</p><p><strong>Availability: </strong>The software ebwt2snp is freely available for academic use at: https://github.com/nicolaprezza/ebwt2snp.</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":" ","pages":"3"},"PeriodicalIF":1.0,"publicationDate":"2019-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-019-0137-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37028905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Constrained incremental tree building: new absolute fast converging phylogeny estimation methods with improved scalability and accuracy.","authors":"Qiuyi Zhang, Satish Rao, Tandy Warnow","doi":"10.1186/s13015-019-0136-9","DOIUrl":"https://doi.org/10.1186/s13015-019-0136-9","url":null,"abstract":"<p><strong>Background: </strong>Absolute fast converging (AFC) phylogeny estimation methods are ones that have been proven to recover the true tree with high probability given sequences whose lengths are polynomial in the number of number of leaves in the tree (once the shortest and longest branch weights are fixed). While there has been a large literature on AFC methods, the best in terms of empirical performance was <math><mrow><mi>D</mi> <mi>C</mi> <msub><mi>M</mi> <mrow><mi>NJ</mi></mrow> </msub> <mo>,</mo></mrow> </math> published in SODA 2001. The main empirical advantage of <math> <msub><mrow><mi>DCM</mi></mrow> <mrow><mi>NJ</mi></mrow> </msub> </math> over other AFC methods is its use of neighbor joining (<i>NJ</i>) to construct trees on smaller taxon subsets, which are then combined into a tree on the full set of species using a supertree method; in contrast, the other AFC methods in essence depend on quartet trees that are computed independently of each other, which reduces accuracy compared to neighbor joining. However, <math> <msub><mrow><mi>DCM</mi></mrow> <mrow><mi>NJ</mi></mrow> </msub> </math> is unlikely to scale to large datasets due to its reliance on supertree methods, as no current supertree methods are able to scale to large datasets with high accuracy.</p><p><strong>Results: </strong>In this study we present a new approach to large-scale phylogeny estimation that shares some of the features of <math> <msub><mrow><mi>DCM</mi></mrow> <mrow><mi>NJ</mi></mrow> </msub> </math> but bypasses the use of supertree methods. We prove that this new approach is AFC and uses polynomial time and space. Furthermore, we describe variations on this basic approach that can be used with leaf-disjoint constraint trees (computed using methods such as maximum likelihood) to produce other methods that are likely to provide even better accuracy. Thus, we present a new generalizable technique for large-scale tree estimation that is designed to improve scalability for phylogeny estimation methods to ultra-large datasets, and that can be used in a variety of settings (including tree estimation from unaligned sequences, and species tree estimation from gene trees).</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":" ","pages":"2"},"PeriodicalIF":1.0,"publicationDate":"2019-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-019-0136-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37204080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin S Engler, Bertrand Caron, Lourens Veen, Daan P Geerke, Alan E Mark, Gunnar W Klau
{"title":"Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach.","authors":"Martin S Engler, Bertrand Caron, Lourens Veen, Daan P Geerke, Alan E Mark, Gunnar W Klau","doi":"10.1186/s13015-019-0138-7","DOIUrl":"https://doi.org/10.1186/s13015-019-0138-7","url":null,"abstract":"<p><p>A key factor in computational drug design is the consistency and reliability with which intermolecular interactions between a wide variety of molecules can be described. Here we present a procedure to efficiently, reliably and automatically assign partial atomic charges to atoms based on known distributions. We formally introduce the molecular charge assignment problem, where the task is to select a charge from a set of candidate charges for every atom of a given query molecule. Charges are accompanied by a score that depends on their observed frequency in similar neighbourhoods (chemical environments) in a database of previously parameterised molecules. The aim is to assign the charges such that the total charge equals a known target charge within a margin of error while maximizing the sum of the charge scores. We show that the problem is a variant of the well-studied multiple-choice knapsack problem and thus weakly <math><mi>NP</mi></math> -complete. We propose solutions based on Integer Linear Programming and a pseudo-polynomial time Dynamic Programming algorithm. We demonstrate that the results obtained for novel molecules not included in the database are comparable to the ones obtained performing explicit charge calculations while decreasing the time to determine partial charges for a molecule from hours or even days to below a second. Our software is openly available.</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":" ","pages":"1"},"PeriodicalIF":1.0,"publicationDate":"2019-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-019-0138-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37030172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Morten Muhlig Nielsen, Paula Tataru, Tobias Madsen, Asger Hobolth, Jakob Skou Pedersen
{"title":"Regmex: a statistical tool for exploring motifs in ranked sequence lists from genomics experiments.","authors":"Morten Muhlig Nielsen, Paula Tataru, Tobias Madsen, Asger Hobolth, Jakob Skou Pedersen","doi":"10.1186/s13015-018-0135-2","DOIUrl":"https://doi.org/10.1186/s13015-018-0135-2","url":null,"abstract":"<p><strong>Background: </strong>Motif analysis methods have long been central for studying biological function of nucleotide sequences. Functional genomics experiments extend their potential. They typically generate sequence lists ranked by an experimentally acquired functional property such as gene expression or protein binding affinity. Current motif discovery tools suffer from limitations in searching large motif spaces, and thus more complex motifs may not be included. There is thus a need for motif analysis methods that are tailored for analyzing specific complex motifs motivated by biological questions and hypotheses rather than acting as a screen based motif finding tool.</p><p><strong>Methods: </strong>We present Regmex (REGular expression Motif EXplorer), which offers several methods to identify overrepresented motifs in ranked lists of sequences. Regmex uses regular expressions to define motifs or families of motifs and embedded Markov models to calculate exact p-values for motif observations in sequences. Biases in motif distributions across ranked sequence lists are evaluated using random walks, Brownian bridges, or modified rank based statistics. A modular setup and fast analytic <i>p</i> value evaluations make Regmex applicable to diverse and potentially large-scale motif analysis problems.</p><p><strong>Results: </strong>We demonstrate use cases of combined motifs on simulated data and on expression data from micro RNA transfection experiments. We confirm previously obtained results and demonstrate the usability of Regmex to test a specific hypothesis about the relative location of microRNA seed sites and U-rich motifs. We further compare the tool with an existing motif discovery tool and show increased sensitivity.</p><p><strong>Conclusions: </strong>Regmex is a useful and flexible tool to analyze motif hypotheses that relates to large data sets in functional genomics. The method is available as an R package (https://github.com/muhligs/regmex).</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":"13 ","pages":"17"},"PeriodicalIF":1.0,"publicationDate":"2018-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-018-0135-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36831399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Superbubbles revisited.","authors":"Fabian Gärtner, Lydia Müller, Peter F Stadler","doi":"10.1186/s13015-018-0134-3","DOIUrl":"https://doi.org/10.1186/s13015-018-0134-3","url":null,"abstract":"<p><strong>Background: </strong>Superbubbles are distinctive subgraphs in direct graphs that play an important role in assembly algorithms for high-throughput sequencing (HTS) data. Their practical importance derives from the fact they are connected to their host graph by a single entrance and a single exit vertex, thus allowing them to be handled independently. Efficient algorithms for the enumeration of superbubbles are therefore of important for the processing of HTS data. Superbubbles can be identified within the strongly connected components of the input digraph after transforming them into directed acyclic graphs. The algorithm by Sung et al. (IEEE ACM Trans Comput Biol Bioinform 12:770-777, 2015) achieves this task in <math><mrow><mi>O</mi> <mo>(</mo> <mi>m</mi> <mspace></mspace> <mi>l</mi> <mi>o</mi> <mi>g</mi> <mo>(</mo> <mi>m</mi> <mo>)</mo> <mo>)</mo></mrow> </math> -time. The extraction of superbubbles from the transformed components was later improved to by Brankovic et al. (Theor Comput Sci 609:374-383, 2016) resulting in an overall <math><mrow><mi>O</mi> <mo>(</mo> <mi>m</mi> <mo>+</mo> <mi>n</mi> <mo>)</mo></mrow> </math> -time algorithm.</p><p><strong>Results: </strong>A re-analysis of the mathematical structure of superbubbles showed that the construction of auxiliary DAGs from the strongly connected components in the work of Sung et al. missed some details that can lead to the reporting of false positive superbubbles. We propose an alternative, even simpler auxiliary graph that solved the problem and retains the linear running time for general digraph. Furthermore, we describe a simpler, space-efficient <math><mrow><mi>O</mi> <mo>(</mo> <mi>m</mi> <mo>+</mo> <mi>n</mi> <mo>)</mo></mrow> </math> -time algorithm for detecting superbubbles in DAGs that uses only simple data structures.</p><p><strong>Implementation: </strong>We present a reference implementation of the algorithm that accepts many commonly used formats for the input graph and provides convenient access to the improved algorithm. https://github.com/Fabianexe/Superbubble.</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":"13 ","pages":"16"},"PeriodicalIF":1.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-018-0134-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36755754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yves Frank, Tomas Hruz, Thomas Tschager, Valentin Venzin
{"title":"Improved de novo peptide sequencing using LC retention time information.","authors":"Yves Frank, Tomas Hruz, Thomas Tschager, Valentin Venzin","doi":"10.1186/s13015-018-0132-5","DOIUrl":"https://doi.org/10.1186/s13015-018-0132-5","url":null,"abstract":"<p><strong>Background: </strong>Liquid chromatography combined with tandem mass spectrometry is an important tool in proteomics for peptide identification. Liquid chromatography temporally separates the peptides in a sample. The peptides that elute one after another are analyzed via tandem mass spectrometry by measuring the mass-to-charge ratio of a peptide and its fragments. De novo peptide sequencing is the problem of reconstructing the amino acid sequences of a peptide from this measurement data. Past de novo sequencing algorithms solely consider the mass spectrum of the fragments for reconstructing a sequence.</p><p><strong>Results: </strong>We propose to additionally exploit the information obtained from liquid chromatography. We study the problem of computing a sequence that is not only in accordance with the experimental mass spectrum, but also with the chromatographic retention time. We consider three models for predicting the retention time and develop algorithms for de novo sequencing for each model.</p><p><strong>Conclusions: </strong>Based on an evaluation for two prediction models on experimental data from synthesized peptides we conclude that the identification rates are improved by exploiting the chromatographic information. In our evaluation, we compare our algorithms using the retention time information with algorithms using the same scoring model, but not the retention time.</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":"13 ","pages":"14"},"PeriodicalIF":1.0,"publicationDate":"2018-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-018-0132-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36459456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andre R Oliveira, Guillaume Fertin, Ulisses Dias, Zanoni Dias
{"title":"Sorting signed circular permutations by super short operations.","authors":"Andre R Oliveira, Guillaume Fertin, Ulisses Dias, Zanoni Dias","doi":"10.1186/s13015-018-0131-6","DOIUrl":"https://doi.org/10.1186/s13015-018-0131-6","url":null,"abstract":"<p><strong>Background: </strong>One way to estimate the evolutionary distance between two given genomes is to determine the minimum number of large-scale mutations, or <i>genome rearrangements</i>, that are necessary to transform one into the other. In this context, genomes can be represented as ordered sequences of genes, each gene being represented by a signed integer. If no gene is repeated, genomes are thus modeled as signed permutations of the form <math><mrow><mi>π</mi><mo>=</mo><mo>(</mo><msub><mi>π</mi><mn>1</mn></msub><msub><mi>π</mi><mn>2</mn></msub><mo>…</mo><msub><mi>π</mi><mi>n</mi></msub><mo>)</mo></mrow></math> , and in that case we can consider without loss of generality that one of them is the identity permutation <math><mrow><msub><mi>ι</mi><mi>n</mi></msub><mo>=</mo><mrow><mo>(</mo><mn>12</mn><mo>…</mo><mi>n</mi><mo>)</mo></mrow></mrow></math> , and that we just need to <i>sort</i> the other (i.e., transform it into <math><msub><mi>ι</mi><mi>n</mi></msub></math> ). The most studied genome rearrangement events are <i>reversals</i>, where a segment of the genome is reversed and reincorporated at the same location; and <i>transpositions</i>, where two consecutive segments are exchanged. Many variants, e.g., combining different types of (possibly constrained) rearrangements, have been proposed in the literature. One of them considers that the number of genes involved, in a reversal or a transposition, is never greater than two, which is known as the problem of sorting by <i>super short operations</i> (or SSOs).</p><p><strong>Results and conclusions: </strong>All problems considering SSOs in permutations have been shown to be in <math><mi>P</mi></math> , except for one, namely sorting signed circular permutations by super short reversals and super short transpositions. Here we fill this gap by introducing a new graph structure called <i>cyclic permutation graph</i> and providing a series of intermediate results, which allows us to design a polynomial algorithm for sorting signed circular permutations by super short reversals and super short transpositions.</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":"13 ","pages":"13"},"PeriodicalIF":1.0,"publicationDate":"2018-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-018-0131-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36360826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Split-inducing indels in phylogenomic analysis.","authors":"Alexander Donath, Peter F Stadler","doi":"10.1186/s13015-018-0130-7","DOIUrl":"https://doi.org/10.1186/s13015-018-0130-7","url":null,"abstract":"<p><strong>Background: </strong>Most phylogenetic studies using molecular data treat gaps in multiple sequence alignments as missing data or even completely exclude alignment columns that contain gaps.</p><p><strong>Results: </strong>Here we show that gap patterns in large-scale, genome-wide alignments are themselves phylogenetically informative and can be used to infer reliable phylogenies provided the gap data are properly filtered to reduce noise introduced by the alignment method. We introduce here the notion of split-inducing indels (<i>splids</i>) that define an approximate bipartition of the taxon set. We show both in simulated data and in case studies on real-life data that <i>splids</i> can be efficiently extracted from phylogenomic data sets.</p><p><strong>Conclusions: </strong>Suitably processed gap patterns extracted from genome-wide alignment provide a surprisingly clear phylogenetic signal and an allow the inference of accurate phylogenetic trees.</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":"13 ","pages":"12"},"PeriodicalIF":1.0,"publicationDate":"2018-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-018-0130-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36328089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michał Aleksander Ciach, Anna Muszewska, Paweł Górecki
{"title":"Locus-aware decomposition of gene trees with respect to polytomous species trees.","authors":"Michał Aleksander Ciach, Anna Muszewska, Paweł Górecki","doi":"10.1186/s13015-018-0128-1","DOIUrl":"https://doi.org/10.1186/s13015-018-0128-1","url":null,"abstract":"<p><strong>Background: </strong>Horizontal gene transfer (HGT), a process of acquisition and fixation of foreign genetic material, is an important biological phenomenon. Several approaches to HGT inference have been proposed. However, most of them either rely on approximate, non-phylogenetic methods or on the tree reconciliation, which is computationally intensive and sensitive to parameter values.</p><p><strong>Results: </strong>We investigate the locus tree inference problem as a possible alternative that combines the advantages of both approaches. We present several algorithms to solve the problem in the parsimony framework. We introduce a novel tree mapping, which allows us to obtain a heuristic solution to the problems of locus tree inference and duplication classification.</p><p><strong>Conclusions: </strong>Our approach allows for faster comparisons of gene and species trees and improves known algorithms for duplication inference in the presence of polytomies in the species trees. We have implemented our algorithms in a software tool available at https://github.com/mciach/LocusTreeInference.</p>","PeriodicalId":50823,"journal":{"name":"Algorithms for Molecular Biology","volume":"13 ","pages":"11"},"PeriodicalIF":1.0,"publicationDate":"2018-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13015-018-0128-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36204242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}