Maximum likelihood models and algorithms for gene tree evolution with duplications and losses

Background

The abundance of new genomic data provides the opportunity to map the location of gene duplication and loss events on a species phylogeny. The first methods for mapping gene duplications and losses were based on a parsimony criterion, finding the mapping that minimizes the number of duplication and loss events. Probabilistic modeling of gene duplication and loss is relatively new and has largely focused on birth-death processes.

Results

We introduce a new maximum likelihood model that estimates the speciation and gene duplication and loss events in a gene tree within a species tree with branch lengths. We also provide an, in practice, efficient algorithm that computes optimal evolutionary scenarios for this model. We implemented the algorithm in the program DrML and verified its performance with empirical and simulated data.

Conclusions

In test data sets, DrML finds optimal gene duplication and loss scenarios within minutes, even when the gene trees contain sequences from several hundred species. In many cases, these optimal scenarios differ from the lca-mapping that results from a parsimony gene tree reconciliation. Thus, DrML provides a new, practical statistical framework on which to study gene duplication.

     

GATC: a genetic algorithm for gene tree construction under the Duplication-Transfer-Loss model of evolution

Background

Several methods have been developed for the accurate reconstruction of gene trees. Some of them use reconciliation with a species tree to correct, a posteriori, errors in gene trees inferred from multiple sequence alignments. Unfortunately the best fit to sequence information can be lost during this process.

Results

We describe GATC, a new algorithm for reconstructing a binary gene tree with branch length. GATC returns optimal solutions according to a measure combining both tree likelihood (according to sequence evolution) and a reconciliation score under the Duplication-Transfer-Loss (DTL) model. It can either be used to construct a gene tree from scratch or to correct trees infered by existing reconstruction method, making it highly flexible to various input data types. The method is based on a genetic algorithm acting on a population of trees at each step. It substantially increases the efficiency of the phylogeny space exploration, reducing the risk of falling into local minima, at a reasonable computational time. We have applied GATC to a dataset of simulated cyanobacterial phylogenies, as well as to an empirical dataset of three reference gene families, and showed that it is able to improve gene tree reconstructions compared with current state-of-the-art algorithms.

Conclusion

The proposed algorithm is able to accurately reconstruct gene trees and is highly suitable for the construction of reference trees. Our results also highlight the efficiency of multi-objective optimization algorithms for the gene tree reconstruction problem. GATC is available on Github at: https://github.com/UdeM-LBIT/GATC.

     

Locus-aware decomposition of gene trees with respect to polytomous species trees

Background

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.

Results

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.

Conclusions

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.

     

Towards sub-quadratic time and space complexity solutions for the dated tree reconciliation problem

Background

Recent coevolutionary analysis has considered tree topology as a means to reduce the asymptotic complexity associated with inferring the complex coevolutionary interrelationships that arise between phylogenetic trees. Targeted algorithmic design for specific tree topologies has to date been highly successful, with one recent formulation providing a logarithmic space complexity reduction for the dated tree reconciliation problem.

Methods

In this work we build on this prior analysis providing a further asymptotic space reduction, by providing a new formulation for the dynamic programming table used by a number of popular coevolutionary analysis techniques. This model gives rise to a sub quadratic running time solution for the dated tree reconciliation problem for selected tree topologies, and is shown to be, in practice, the fastest method for solving the dated tree reconciliation problem for expected evolutionary trees. This result is achieved through the analysis of not only the topology of the trees considered for coevolutionary analysis, but also the underlying structure of the dynamic programming algorithms that are traditionally applied to such analysis.

Conclusion

The newly inferred theoretical complexity bounds introduced herein are then validated using a combination of synthetic and biological data sets, where the proposed model is shown to provide an \(O(\sqrt{n})\) space saving, while it is observed to run in half the time compared to the fastest known algorithm for solving the dated tree reconciliation problem. What is even more significant is that the algorithm derived herein is able to guarantee the optimality of its inferred solution, something that algorithms of comparable speed have to date been unable to achieve.

     

Time-consistent reconciliation maps and forbidden time travel

Background

In the absence of horizontal gene transfer it is possible to reconstruct the history of gene families from empirically determined orthology relations, which are equivalent to event-labeled gene trees. Knowledge of the event labels considerably simplifies the problem of reconciling a gene tree T with a species trees S, relative to the reconciliation problem without prior knowledge of the event types. It is well-known that optimal reconciliations in the unlabeled case may violate time-consistency and thus are not biologically feasible. Here we investigate the mathematical structure of the event labeled reconciliation problem with horizontal transfer.

Results

We investigate the issue of time-consistency for the event-labeled version of the reconciliation problem, provide a convenient axiomatic framework, and derive a complete characterization of time-consistent reconciliations. This characterization depends on certain weak conditions on the event-labeled gene trees that reflect conditions under which evolutionary events are observable at least in principle. We give an \(\mathcal {O}(|V(T)|\log (|V(S)|))\)-time algorithm to decide whether a time-consistent reconciliation map exists. It does not require the construction of explicit timing maps, but relies entirely on the comparably easy task of checking whether a small auxiliary graph is acyclic. The algorithms are implemented in C++ using the boost graph library and are freely available at https://github.com/Nojgaard/tc-recon.

Significance

The combinatorial characterization of time consistency and thus biologically feasible reconciliation is an important step towards the inference of gene family histories with horizontal transfer from orthology data, i.e., without presupposed gene and species trees. The fast algorithm to decide time consistency is useful in a broader context because it constitutes an attractive component for all tools that address tree reconciliation problems.

     

DTL reconciliation repair

Background

Maximum parsimony phylogenetic tree reconciliation is an important technique for reconstructing the evolutionary histories of hosts and parasites, genes and species, and other interdependent pairs. Since the problem of finding temporally feasible maximum parsimony reconciliations is NP-complete, current methods use either exact algorithms with exponential worst-case running time or heuristics that do not guarantee optimal solutions.

Results

We offer an efficient new approach that begins with a potentially infeasible maximum parsimony reconciliation and iteratively “repairs” it until it becomes temporally feasible.

Conclusions

In a non-trivial number of cases, this approach finds solutions that are better than those found by the widely-used Jane heuristic.

     

OCTAL: Optimal Completion of gene trees in polynomial time

Background

For a combination of reasons (including data generation protocols, approaches to taxon and gene sampling, and gene birth and loss), estimated gene trees are often incomplete, meaning that they do not contain all of the species of interest. As incomplete gene trees can impact downstream analyses, accurate completion of gene trees is desirable.

Results

We introduce the Optimal Tree Completion problem, a general optimization problem that involves completing an unrooted binary tree (i.e., adding missing leaves) so as to minimize its distance from a reference tree on a superset of the leaves. We present OCTAL, an algorithm that finds an optimal solution to this problem when the distance between trees is defined using the Robinson–Foulds (RF) distance, and we prove that OCTAL runs in \(O(n^2)\) time, where n is the total number of species. We report on a simulation study in which gene trees can differ from the species tree due to incomplete lineage sorting, and estimated gene trees are completed using OCTAL with a reference tree based on a species tree estimated from the multi-locus dataset. OCTAL produces completed gene trees that are closer to the true gene trees than an existing heuristic approach in ASTRAL-II, but the accuracy of a completed gene tree computed by OCTAL depends on how topologically similar the reference tree (typically an estimated species tree) is to the true gene tree.

Conclusions

OCTAL is a useful technique for adding missing taxa to incomplete gene trees and provides good accuracy under a wide range of model conditions. However, results show that OCTAL’s accuracy can be reduced when incomplete lineage sorting is high, as the reference tree can be far from the true gene tree. Hence, this study suggests that OCTAL would benefit from using other types of reference trees instead of species trees when there are large topological distances between true gene trees and species trees.

     

Biologically feasible gene trees,reconciliation maps and informative triples

Background

The history of gene families—which are equivalent to event-labeled gene trees—can be reconstructed from empirically estimated evolutionary event-relations containing pairs of orthologous, paralogous or xenologous genes. The question then arises as whether inferred event-labeled gene trees are biologically feasible, that is, if there is a possible true history that would explain a given gene tree. In practice, this problem is boiled down to finding a reconciliation map—also known as DTL-scenario—between the event-labeled gene trees and a (possibly unknown) species tree.

Results

In this contribution, we first characterize whether there is a valid reconciliation map for binary event-labeled gene trees T that contain speciation, duplication and horizontal gene transfer events and some unknown species tree S in terms of “informative” triples that are displayed in T and provide information of the topology of S. These informative triples are used to infer the unknown species tree S for T. We obtain a similar result for non-binary gene trees. To this end, however, the reconciliation map needs to be further restricted. We provide a polynomial-time algorithm to decide whether there is a species tree for a given event-labeled gene tree, and in the positive case, to construct the species tree and the respective (restricted) reconciliation map. However, informative triples as well as DTL-scenarios have their limitations when they are used to explain the biological feasibility of gene trees. While reconciliation maps imply biological feasibility, we show that the converse is not true in general. Moreover, we show that informative triples neither provide enough information to characterize “relaxed” DTL-scenarios nor non-restricted reconciliation maps for non-binary biologically feasible gene trees.

     

Anchoring quartet-based phylogenetic distances and applications to species tree reconstruction

Background

Inferring species trees from gene trees using the coalescent-based summary methods has been the subject of much attention, yet new scalable and accurate methods are needed.

Results

We introduce DISTIQUE, a new statistically consistent summary method for inferring species trees from gene trees under the coalescent model. We generalize our results to arbitrary phylogenetic inference problems; we show that two arbitrarily chosen leaves, called anchors, can be used to estimate relative distances between all other pairs of leaves by inferring relevant quartet trees. This results in a family of distance-based tree inference methods, with running times ranging between quadratic to quartic in the number of leaves.

Conclusions

We show in simulated studies that DISTIQUE has comparable accuracy to leading coalescent-based summary methods and reduced running times.

     

Analysis of long branch extraction and long branch shortening

Background

Long branch attraction (LBA) is a problem that afflicts both the parsimony and maximum likelihood phylogenetic analysis techniques. Research has shown that parsimony is particularly vulnerable to inferring the wrong tree in Felsenstein topologies. The long branch extraction method is a procedure to detect a data set suffering from this problem so that Maximum Likelihood could be used instead of Maximum Parsimony.

Results

The long branch extraction method has been well cited and used by many authors in their analysis but no strong validation has been performed as to its accuracy. We performed such an analysis by an extensive search of the branch length search space under two topologies of six taxa, a Felsenstein-like topology and Farris-like topology. We also examine a long branch shortening method.

Conclusions

The long branch extraction method seems to mask the majority of the search space rendering it ineffective as a detection method of LBA. A proposed alternative, the long branch shortening method, is also ineffective in predicting long branch attraction for all tree topologies.

     

Inferring angiosperm phylogeny from EST data with widespread gene duplication

Background

Most studies inferring species phylogenies use sequences from single copy genes or sets of orthologs culled from gene families. For taxa such as plants, with very high levels of gene duplication in their nuclear genomes, this has limited the exploitation of nuclear sequences for phylogenetic studies, such as those available in large EST libraries. One rarely used method of inference, gene tree parsimony, can infer species trees from gene families undergoing duplication and loss, but its performance has not been evaluated at a phylogenomic scale for EST data in plants.

Results

A gene tree parsimony analysis based on EST data was undertaken for six angiosperm model species and Pinus, an outgroup. Although a large fraction of the tentative consensus sequences obtained from the TIGR database of ESTs was assembled into homologous clusters too small to be phylogenetically informative, some 557 clusters contained promising levels of information. Based on maximum likelihood estimates of the gene trees obtained from these clusters, gene tree parsimony correctly inferred the accepted species tree with strong statistical support. A slight variant of this species tree was obtained when maximum parsimony was used to infer the individual gene trees instead.

Conclusion

Despite the complexity of the EST data and the relatively small fraction eventually used in inferring a species tree, the gene tree parsimony method performed well in the face of very high apparent rates of duplication.

     

A clique-based method for the edit distance between unordered trees and its application to analysis of glycan structures

Background

Measuring similarities between tree structured data is important for analysis of RNA secondary structures, phylogenetic trees, glycan structures, and vascular trees. The edit distance is one of the most widely used measures for comparison of tree structured data. However, it is known that computation of the edit distance for rooted unordered trees is NP-hard. Furthermore, there is almost no available software tool that can compute the exact edit distance for unordered trees.

Results

In this paper, we present a practical method for computing the edit distance between rooted unordered trees. In this method, the edit distance problem for unordered trees is transformed into the maximum clique problem and then efficient solvers for the maximum clique problem are applied. We applied the proposed method to similar structure search for glycan structures. The result suggests that our proposed method can efficiently compute the edit distance for moderate size unordered trees. It also suggests that the proposed method has the accuracy comparative to those by the edit distance for ordered trees and by an existing method for glycan search.

Conclusions

The proposed method is simple but useful for computation of the edit distance between unordered trees. The object code is available upon request.

     

An ILP solution for the gene duplication problem

Background

The gene duplication (GD) problem seeks a species tree that implies the fewest gene duplication events across a given collection of gene trees. Solving this problem makes it possible to use large gene families with complex histories of duplication and loss to infer phylogenetic trees. However, the GD problem is NP-hard, and therefore, most analyses use heuristics that lack any performance guarantee.

Results

We describe the first integer linear programming (ILP) formulation to solve instances of the gene duplication problem exactly. With simulations, we demonstrate that the ILP solution can solve problem instances with up to 14 taxa. Furthermore, we apply the new ILP solution to solve the gene duplication problem for the seed plant phylogeny using a 12-taxon, 6, 084-gene data set. The unique, optimal solution, which places Gnetales sister to the conifers, represents a new, large-scale genomic perspective on one of the most puzzling questions in plant systematics.

Conclusions

Although the GD problem is NP-hard, our novel ILP solution for it can solve instances with data sets consisting of as many as 14 taxa and 1, 000 genes in a few hours. These are the largest instances that have been solved to optimally to date. Thus, this work can provide large-scale genomic perspectives on phylogenetic questions that previously could only be addressed by heuristic estimates.

     

Root fungal colonisations of the understory grass <Emphasis Type="Italic">Deschampsia flexuosa</Emphasis> after top-canopy harvesting

Aims

Root fungal relationships in forest understory may be affected by tree harvesting. Deschampsia flexuosa forms a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi functioning in nutrient uptake, and a more loose association with dark septate endophytic (DSE) fungi. We asked how harvesting affects fungal colonisations and whether DSE is more prone to change than AM.

Methods

Deschampsia flexuosa plants were sampled close to a control or a cut tree after top-canopy harvesting in a primary successional site. Colonisations were studied using light microscopy. Shoot N%, vegetation cover and soil nutrients were determined.

Results

Tree harvesting did not affect vegetation and soil parameters, except potassium (K⁺) increasing near cut trees. AM colonisation did not change, while DSE increased. Shoot N% increased with increasing DSE near cut trees. Hyaline septate (HSE) hyphae and soil K⁺ and magnesium (Mg²⁺) were positively correlated near control trees. Lichen cover and HSE correlated negatively.

Conclusions

DSE colonisation increased but AM did not change after harvesting. Positive correlation of DSE with shoot N% near cut trees may suggest a role for DSE in favouring plant nitrogen uptake after disturbance in an open microsite. HSE may play a role in K⁺ and Mg²⁺ uptake.

     

Tree-microbial biomass competition for nutrients in a temperate deciduous forest,central Germany

Aims

Our goals were (1) to determine whether tree species diversity affects nutrient (N, P and K) cycling, and (2) to assess whether there is competition for these nutrients between microbial biomass and trees.

Methods

We measured nutrient resorption efficiency by trees, nutrient contents in leaf litterfall, decomposition rates of leaf litter, nutrient turnover in decomposing leaf litter, and plant-available nutrients in the soil in mono-species stands of beech, oak, hornbeam and lime and in mixed-species stands, each consisting of three of these species.

Results

Cycling of nutrients through leaf litter input and decomposition were influenced by the types of tree species and not simply by tree species diversity. Trees and microbial biomass were competing strongly for P, less for K and only marginally for N. Such competition was most pronounced in mono-species stands of beech and oak, which had low nutrient turnover in their slow decomposing leaf litter, and less in mono-species stands of hornbeam and lime, which had high nutrient turnover in their fast decomposing leaf litter.

Conclusions

The low soil P and K availability in beech stands, which limit the growth of beech at Hainich, Germany, were alleviated by mixing beech with hornbeam and lime. These species-specific effects on nutrient cycling and soil nutrient availability can aid forest management in improving productivity and soil fertility.

     

Fine-root growth in a forested bog is seasonally dynamic,but shallowly distributed in nutrient-poor peat

Background and aims

Fine roots contribute to ecosystem carbon, water, and nutrient fluxes through resource acquisition, respiration, exudation, and turnover, but are understudied in peatlands. We aimed to determine how the amount and timing of fine-root growth in a forested, ombrotrophic bog varied across gradients of vegetation density, peat microtopography, and changes in environmental conditions across the growing season and throughout the peat profile.

Methods

We quantified fine-root peak standing crop and growth using non-destructive minirhizotron technology over a two-year period, focusing on the dominant woody species in the bog: Picea mariana, Larix laricina, Rhododendron groenlandicum, and Chamaedaphne calyculata.

Results

The fine roots of trees and shrubs were concentrated in raised hummock microtopography, with more tree roots associated with greater tree densities and a unimodal peak in shrub roots at intermediate tree densities. Fine-root growth tended to be seasonally dynamic, but shallowly distributed, in a thin layer of nutrient-poor, aerobic peat above the growing season water table level.

Conclusions

The dynamics and distribution of fine roots in this forested ombrotrophic bog varied across space and time in response to biological, edaphic, and climatic conditions, and we expect these relationships to be sensitive to projected environmental changes in northern peatlands.

     

Statistical analysis of fractionation resistance by functional category and expression

Background

The current literature establishes the importance of gene functional category and expression in promoting or suppressing duplicate gene loss after whole genome doubling in plants, a process known as fractionation. Inspired by studies that have reported gene expression to be the dominating factor in preventing duplicate gene loss, we analyzed the relative effect of functional category and expression.

Methods

We use multivariate methods to study data sets on gene retention, function and expression in rosids and asterids to estimate effects and assess their interaction.

Results

Our results suggest that the effect on duplicate gene retention fractionation by functional category and expression are independent and have no statistical interaction.

Conclusion

In plants, functional category is the more dominant factor in explaining duplicate gene loss.

     

Identification of cancer subtypes from single-cell RNA-seq data using a consensus clustering method

Background

Human cancers are complex ecosystems composed of cells with distinct molecular signatures. Such intratumoral heterogeneity poses a major challenge to cancer diagnosis and treatment. Recent advancements of single-cell techniques such as scRNA-seq have brought unprecedented insights into cellular heterogeneity. Subsequently, a challenging computational problem is to cluster high dimensional noisy datasets with substantially fewer cells than the number of genes.

Methods

In this paper, we introduced a consensus clustering framework conCluster, for cancer subtype identification from single-cell RNA-seq data. Using an ensemble strategy, conCluster fuses multiple basic partitions to consensus clusters.

Results

Applied to real cancer scRNA-seq datasets, conCluster can more accurately detect cancer subtypes than the widely used scRNA-seq clustering methods. Further, we conducted co-expression network analysis for the identified melanoma subtypes.

Conclusions

Our analysis demonstrates that these subtypes exhibit distinct gene co-expression networks and significant gene sets with different functional enrichment.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

PnpProbs: a better multiple sequence alignment tool by better handling of guide trees

Background

This paper describes a new MSA tool called PnpProbs, which constructs better multiple sequence alignments by better handling of guide trees. It classifies sequences into two types: normally related and distantly related. For normally related sequences, it uses an adaptive approach to construct the guide tree needed for progressive alignment; it first estimates the input’s discrepancy by computing the standard deviation of their percent identities, and based on this estimate, it chooses the better method to construct the guide tree. For distantly related sequences, PnpProbs abandons the guide tree and uses instead some non-progressive alignment method to generate the alignment.

Results

To evaluate PnpProbs, we have compared it with thirteen other popular MSA tools, and PnpProbs has the best alignment scores in all but one test. We have also used it for phylogenetic analysis, and found that the phylogenetic trees constructed from PnpProbs’ alignments are closest to the model trees.

Conclusions

By combining the strength of the progressive and non-progressive alignment methods, we have developed an MSA tool called PnpProbs. We have compared PnpProbs with thirteen other popular MSA tools and our results showed that our tool usually constructed the best alignments.