GeoPhy: Differentiable Phylogenetic Inference via Geometric Gradients of Tree Topologies

Phylogenetic inference, grounded in molecular evolution models, is essential for understanding the evolutionary relationships in biological data. Accounting for the uncertainty of phylogenetic tree variables, which include tree topologies and evolutionary distances on branches, is crucial for accurately inferring species relationships from molecular data and tasks requiring variable marginalization. Variational Bayesian methods are key to developing scalable, practical models; however, it remains challenging to conduct phylogenetic inference without restricting the combinatorially vast number of possible tree topologies. In this work, we introduce a novel, fully differentiable formulation of phylogenetic inference that leverages a unique representation of topological distributions in continuous geometric spaces. Through practical considerations on design spaces and control variates for gradient estimations, our approach, GeoPhy, enables variational inference without limiting the topological candidates. In experiments using real benchmark datasets, GeoPhy significantly outperformed other approximate Bayesian methods that considered whole topologies.

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Peer review

Reviewer Wg7V7/10 · confidence 4/52023-06-25

Summary

This work presents a new robust and scalable method for inferring phylogenetic trees based on (variational) Bayesian inference.

Strengths

Originality - the originality of this work is in providing a robust and rigorous solution to an important application problem where the application of Bayesian methodology has so far been relatively limited Quality - the work is well motivated and appropriately implemented including the relevant derivations and experimental benchmarking Clarity - language is fluent, and intuitive illustrations support reading; the technical details are described in sufficient detail and complemented by intuitive explanation. Conclucions and limitations are clearly stated. Significance - significant, general and timely application problem addressed - improved robustness, while maintaining scalability that allows practical application

Weaknesses

Treatment of the benchmark data sets is limited compared to the potential of the method for real applications. This could be expanded to highlight the relevance of the work.

Questions

Good performance compared to alternatives is shown but is it possible to demonstrate more on practical relevance for this?

Rating

7: Accept: Technically solid paper, with high impact on at least one sub-area, or moderate-to-high impact on more than one areas, with good-to-excellent evaluation, resources, reproducibility, and no unaddressed ethical considerations.

Confidence

4: You are confident in your assessment, but not absolutely certain. It is unlikely, but not impossible, that you did not understand some parts of the submission or that you are unfamiliar with some pieces of related work.

Soundness

3 good

Presentation

4 excellent

Contribution

4 excellent

Limitations

No source code. No assessment of societal implications.

Reviewer xhDC3/10 · confidence 2/52023-06-29

Summary

The authors propose a method for learning phylogenetic trees from sequence data. The key idea is borrowed from [16], which is to represent the tree topology in terms of an embedding of the leafs of the trees in a continuous space, $z \in \mathcal{Z}$ from which the topology is extracted via a mapping $\tau \;:\; \mathcal{Z} \to \mathcal{T}$, where $\mathcal{T}$ is the space of binary trees, using a distance-based technique (in particular the popular Neighbor-Joining (NJ) method). The fact that the representation in terms of $z$ is continuous has benefits in a variational representation of the posterior distribution over trees. The theoretical contribution of the present paper is resolving some issues with "an unevaluated Jacobian determinant between $B_\tau$ and $z$" (see Sec. 4 "Related work", p. 6). The resulting method is demonstrated through simulations, showing that the method yields high-scoring models (high log-likelihoods), but not as high as existing variational and MCMC techniques (Table 2).

Strengths

- I like the idea (which really borrowed from [16], so not really a new idea) of the embedding in terms of continuous coordinates - solid theoretical derivation of the variational estimators - promising results - quite well written (although a bit dense)

Weaknesses

- not clear what the benefits are compared to existing variational and MCMC methods (which are presented as the gold-standard)

Questions

My main question is what are the benefits compared to, e.g., MrBayes, VBPI-GNN, and the method proposed in [33], the first two of which are referred to as gold standard. I'm guessing the proposed method is computationally more efficient and scalable, but this should be clearly demonstrated (or am I missing something?). I should point out that I'm no expert of variational Bayes, so I didn't check the derivations from that point of view. I'm counting on the other reviewers to comment on that side. detailed comments: p. 7: "marginal log-likelihood (MLL) estimates": Does this mean MLL values? I mean, "maximum (log-) likelihood estimate" usually refers to an estimate of a parameter that is obtained by likelihood maximization, so it'd be good to be unambiguous. p. 7: typo "Monte-Calro"

Rating

3: Reject: For instance, a paper with technical flaws, weak evaluation, inadequate reproducibility and incompletely addressed ethical considerations.

Confidence

2: You are willing to defend your assessment, but it is quite likely that you did not understand the central parts of the submission or that you are unfamiliar with some pieces of related work. Math/other details were not carefully checked.

Soundness

4 excellent

Presentation

3 good

Contribution

2 fair

Limitations

I think so (but see my question about the benefits wrt. existing methods above).

Reviewer Bru68/10 · confidence 4/52023-07-05

Summary

The authors present a novel variational distribution for tree topologies, $Q(\tau)$, in the context of variational inference (VI) in phylogenetics. They construct their $Q(\tau)$ by introducing a continuous distribution $Q(z)$ in hyperbolic space and define $Q(\tau)$ by an expectation over the support of $Q(z)$ of an indicator function acting on a mapping from the hyperbolic space to the topology space; this allows sampling from $Q(z)$ and reconstructing \tau through the neighbour joining algorithm and, by the differentiable $Q(z)$ distribution, enables Monte-Carlo gradient estimation to maximize the Evidence Lower Bound (ELBO). An ablation study is conducted to evaluate different $Q(z)$ distributions (Normal and Wrapped-Normal) and control variates. The model is then compared to other VI methods and MrBayes across 8 datasets.

Strengths

The problem of phylogenetic tree reconstruction is paramount to understanding evolution, e.g., the evolution of species and cancer. The grand size of the tree topology space induced by a set of taxa constitutes a major obstacle for inference; any method successful in efficient exploration of this space is a significant contribution to the field. Here, the authors construct a differentiable $Q(\tau)$, enabling the use of gradients to indirectly maneuver the tree topology space. Furthermore, the proposed framework does not require restricting the tree topology space based on pre-processing steps as in VBPI. The novel, differentiable approach to $Q(\tau)$, the avoidance of restrictions of the tree support and reporting strong results on datasets DS1-DS8 in terms of the ELBO(Q,R), makes the paper a significant and original contribution to the field of Bayesian phylogenetics.

Weaknesses

The standard deviations of the proposed method reported in Table 2 are low for multiple datasets; this may be due to the consistency of the optimization across seeds, but may also indicate that the support of $Q(z)$ collapses to regions containing one/few unique $\tau(z)$. Since there is no analysis/discussion regarding this, the paper presents limited information regarding the representative power of $Q(\tau)$, which is a major set back of the paper, especially as the MrBayes "golden-run" posteriors over the tree topologies for DS1-DS8 support multiple topologies (Whidden and Matsen 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395846/ ). The use of $Q(z)$ makes the method extra susceptible to limited topology support by the inherent mode-seeking behaviour in VI; while a mode in the topology space could represent multiple tree topologies, a mode in Z-space might only support reconstruction of, at worst, one tree topology. The paper would benefit from reporting runtime compared to MrBayes and other VI methods, especially as one of the strengths in VI is speed. The current report on runtime is limited and is relegated to Appendix C. Furthermore, an obvious weakness is the need to introduce a lower bound of the ELBO.

Questions

The paper is a significant, novel and promising contribution to the field and is in its current format acceptable for publication. However, based on my concerns in the weakness section, addressing the following points in the rebuttal could make me increase my score: 1. A discussion regarding the low variance in Table 2 and limited knowledge of the representative power $Q(\tau)$. 2. Clearer reporting of the runtime of the algorithm in the main paper. Addressing the following points in the rebuttal could increase my score even further: 1. A experiment demonstrating the representative power/limitations of $Q(\tau)$ Some misprints: "Monte-Calro" figure text of Figure 2 line 4.

Rating

8: Strong Accept: Technically strong paper, with novel ideas, excellent impact on at least one area, or high-to-excellent impact on multiple areas, with excellent evaluation, resources, and reproducibility, and no unaddressed ethical considerations.

Confidence

4: You are confident in your assessment, but not absolutely certain. It is unlikely, but not impossible, that you did not understand some parts of the submission or that you are unfamiliar with some pieces of related work.

Soundness

3 good

Presentation

4 excellent

Contribution

4 excellent

Limitations

Limitations has been somewhat discussed (see weaknesses for omitted discussion of possible limitation).

Reviewer MJWZ7/10 · confidence 4/52023-07-07

Summary

Authors proposed GeoPhy as a fully differentiable approach for phylogenetic inference, addressing a fundamental problem in phylogenetic inference. In experiments with real benchmark datasets, GeoPhy demonstrated its superior performance compared to other methods when considering all topological candidates. This approach is of interest to the general ML community.

Strengths

Overall, the manuscript is well-written.

Weaknesses

It is highly recommended to include an algorithm block summarizing the GeoPhy method from input to output for clarity. Additionally, there are some details in the experimental section that need clarification.

Questions

Major questions: 1. In Section 3.1, the neighbor-joining algorithm is defined as the projection from the distance matrix to the tree topology. However, other standard algorithms, such as UPGMA, could be alternative approaches. Have you investigated if the choice of projection leads to different performance in the benchmark tests? 2. Appendix C.5 provides a rough estimation of the running time, but it is unclear how the other baseline models included in the benchmark tests perform in terms of time. Furthermore, how does the algorithm scale as the number of tips and sites increase? Have you observed any trends in the time curve with respect to the number of taxa and sites? 3. In Table 2, GeoPhy achieves superior performance in the benchmark tests based on likelihoods. Did the optimized topologies look significantly different across the different methods? 4. How were the per-step Monte Carlo samples (K) determined in the benchmark tests? There is no clear winner based on Table 1. 5. Could you elaborate on the approaches used to calculate the marginal log-likelihood (MLL) for all the listed methods?

Rating

7: Accept: Technically solid paper, with high impact on at least one sub-area, or moderate-to-high impact on more than one areas, with good-to-excellent evaluation, resources, reproducibility, and no unaddressed ethical considerations.

Confidence

4: You are confident in your assessment, but not absolutely certain. It is unlikely, but not impossible, that you did not understand some parts of the submission or that you are unfamiliar with some pieces of related work.

Soundness

3 good

Presentation

3 good

Contribution

4 excellent

Limitations

Authors briefly mentioned two limitations of the proposed model: 1) Q(z) can be improved to enhance its expressive power, and 2) the computation cost per update step can be optimized to speed up the overall inference process. These practical concerns can be further addressed in future studies.

Reviewer AJKq5/10 · confidence 5/52023-07-18

Summary

This paper proposed a family of implicit distribution over tree topologies which allows support free variational Bayesian phylogenetic inference. The distribution is constructed based on the neighbor joining algorithm which maps a distribution over the tip node vectors to the tree topology space. Both Euclidean and hyperbolic spaces are considered for the tip node distributions. As the resulting distribution over tree topologies is intractable, an auxiliary reverse distribution was introduced which leads to a looser lower bound for optimization. Various gradient estimators were investigated for the tree topology variational parameters optimization. Experiments on a benchmark of real data problems demonstrated the advantage over other variational approaches (mainly sequential monte carlo based) that does not require preselected tree topololgies.

Strengths

1. The paper is written clearly and well organized. The problem of constructing flexible families of distributions over tree topologies is important for the phylogenetic communities and would to of interest to many practitioners. 2. In addition to a careful derivation to the training objective, the authors also investigated different gradient estimators for tree topology variational parameters.

Weaknesses

1. As admitted by the authors, the proposed variational approximation $Q(z)$ and the reverse distribution $R(z|\tau)$ is simple, which may damage the overall approximation quality of the method. 2. In the derivation of the lower bound, the reverse distribution $R(z|\tau)$ needs to satisfy the constraint: the support of $R(z|\tau)$ should be inside the region $\{z: \tau(z)=\tau\}$. 2. In the experiments, it seems that the performance would be really sensitive to the choice of gradient estimators. I wonder if that is related to the small sample size $K$? The marginal likelihood estimates also tends to have large variance in most cases. 3. It may be hard to assess the performance on the tree topology posterior estimation as the distribution is implicit and defined in a rather sutble way.

Questions

1. In equation 10 and equaiton 12, the expection of the last term is actually zero. Any idea why this term is kept there given that other control variates are considered? 2. How many samples are used to compute the marginal likelihood estimates? 3. The current construction of the reverse distribution $R(z|\tau)$ seems not take the constraints $\tau(z)=\tau$ into consideration directly. Would this have a negative impact on performance? 4. I note that only low dimension tip node vectors ($d\leq 4$) are considered in this paper. Would higher dimension embedding be helpful? 5. How about the tree topology approximation given by the implicit distribution? Although it may be hard to estimate the density, one can also report summary statistics from the sampled trees, for example.

Rating

5: Borderline accept: Technically solid paper where reasons to accept outweigh reasons to reject, e.g., limited evaluation. Please use sparingly.

Confidence

5: You are absolutely certain about your assessment. You are very familiar with the related work and checked the math/other details carefully.

Soundness

3 good

Presentation

3 good

Contribution

3 good

Limitations

yes, they do.

Reviewer Wg7V2023-08-15

Review responses

Thank you, the comments have been adequately addressed. My overall scoring remains unaltered.

Reviewer AJKq2023-08-16

Thanks for the reply

Thanks for the reply. The issue with equation 10 and 12 still remains. I think the current form in equation 10 is wrong, the remaining term from the gradient of the entropy is not the last term in equation 10 (which is the score and hence has 0 expectation). As the author admitted, the reverse distribution $R(z|\tau)$ does not take the constraint into consideration, which would lead to potential problems, e.g., the lower bound is not right. The samples from $Q(\tau)$ do not seem to provide good approximation to the exact posterior, this would be a cause of the biased estimate of MLL compared to MrBayes/VBPI-GNN. I will keep the score.

Authorsrebuttal2023-08-17

Clarifications on review points

Thank you for your continued feedback and assessments. > The issue with equation 10 and 12 still remains. I think the current form in equation 10 is wrong, the remaining term from the gradient of the entropy is not the last term in equation 10 (which is the score and hence has 0 expectation) We acknowledge an oversight in our previous rebuttal wherein we mistakenly wrote $\nabla_\theta Q_\theta(z)$ instead of $\nabla_\theta \ln Q_\theta(z)$. It's worth emphasizing that both $\nabla_z \ln Q_\theta(z)$ and $\nabla_\theta \ln Q_\theta(z)$ are referred to as the 'score function' in literature, but we meant the latter in our manuscript. Notably, while $E_{Q_\theta(z)}[ \nabla_z \ln Q_\theta(z) ] = 0$, the expectation $E_{Q_\theta(z)}[\nabla_\theta \ln Q_\theta(z) ]$ is not zero in general. Regarding the transformation of $\mathbb{H}[Q_\theta(z)]$ in Equation 10, we utilized the reparameterization trick as follows: $ \nabla_\theta \mathbb{H}[Q_\theta(z)] = - \nabla_\theta E_{Q_\theta (z)} [ \ln Q_{\theta}(z) ] = - \nabla_\theta E_{p_z(\epsilon_z)}[ \ln Q_{\theta}(h_\theta(\epsilon_z)) ] = - E_{p_z(\epsilon_z)} [ \nabla_{\theta} \ln Q_{\theta}(h_\theta(\epsilon_z)) ]. $ This aligns with the second term of Equation 12. We will include the transformation above in our revised manuscript for more clarity. We hope this addresses the concerns raised. > As the author admitted, the reverse distribution $R(z | \tau)$ does not take the constraint into consideration, which would lead to potential problems, e.g., the lower bound is not right. The samples from $Q(\tau)$ do not seem to provide good approximation to the exact posterior, this would be a cause of the biased estimate of MLL compared to MrBayes/VBPI-GNN. We would like to complement the above arguments as follows: * The optimization target $L[Q, R]$ is still a right lower bound that satisfies $\ln P(Y) \geq L[Q] \geq L[Q, R]$, irrespective of constraints on $R(z | \tau)$. * However, the maximization of $L[Q, R]$ with respect to $Q$ might yield a suboptimal $Q$ if $L[Q, R]$ hasn't been fully maximized with respect to $R$. * Importantly, maximizing $L[Q, R]$ with respect to $R$ will elicit $R$ to satisfy the constraint (i.e., all $z$ in the support of $R(z | \tau)$ satisfies $\tau(z) = \tau$). Thus, it is not imperative to modify our framework to explicitly ensure the constraint for $R$ (except the expressiveness of $R$ to be able to meet the condition). * As we partly discussed in the section "Limitations and Future work", the remaining challenge for further improvement on the quality of posterior approximation $Q(\tau)$ is the introduction of more expressive distribution families for $Q$ as well as $R$. We appreciate the reviewer to shed light on these important points. We will address these points in detail in our revised manuscript.

Reviewer AJKq2023-08-17

Thanks for the clarification on equation 10 and the validity of the lower bound irrespective of the constraints on $R(z|\tau)$. I would suggest a construction of reverse model that satisfies the constraints if possible.

Authorsrebuttal2023-08-17

Response on constraints for the reverse model

Thank you for the confirmation of the above clarifications. > I would suggest a construction of reverse model that satisfies the constraints if possible. Thank you for your suggestion. We agree that directly introducing constraints on the reverse model $R(z | \tau)$ would be valuable, as it could simplify and improve the optimization process. Unfortunately, we suppose that it is not easy to define a family of probability densities for $R(z | \tau)$ so that the constraint is always satisfied because, to our knowledge, neither the boundary nor the area of such support is known for arbitrary $\tau$. However, as we present in additional experiments (Fig. R3 Fourth), it is possible to perform our approach with a link function $\tau(z)$ other than that based on the neighbor-joining (NJ) algorithm. Therefore, it might be also possible to design another link function $\tau(z)$ so that the domain for $\tau(z) = \tau$ is easier to specify. Exploring this avenue could be an interesting direction for future work.

Reviewer Bru62023-08-17

Response rebuttal

Thank you for addressing my concerns raised in the review. I will raise my score to a 7, for now, as the rebuttals added experiments and discussion adequately addresses Q1-1 and Q1-2. However, regarding Q2-1 I still have some questions. Furthermore, I was not aware of the resemblance to [16] pointed out by reviewer xhDC, which changes my assessment on novelty and therefore less prone to raise the score further. Q1-1: I agree, this a plausible explanation for the low variance. Q1-2: Figure R3 more than adequately addresses my concerns. In light of these results, the paper would benefit from mentioning the faster learning runtime of VCSMC and Vaiphy, illustrating the trade-off between high performance but long training runtime approaches (Geophy, VBPI) vs lower performance but short training runtime approaches (Vaiphy, VCSMC). Q2-1: R2 First to third: I don't understand the experiment behind this, is the consensus trees of Geophy and MrBayes are calculated, and then the ELBO measured under this fixed tree setting? What do each dot represent in each plot? What do 'dim' refer to? Could you please provide a more elaborate description of the experiments behind this plot so I can better assess how they address my concerns. R2 Fourth: I think that the DS1 dataset is not preferable for this analysis, as the support of the MrBayes posterior includes few topologies. Datasets DS4 and higher would've been a better selection (see figure 3 of https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395846/). Nonetheless, it does shine some light on the representative power of $Q(\tau)$ and is a good addition to the paper. Furthermore, what in R2 First-Fourth informs the diversity of the trees sampled by $Q(\tau)$? How many unique trees are used to construct the consensus-tree?

Authorsrebuttal2023-08-19

Response on the remaining concerns

We sincerely appreciate your detailed feedback and the time you've taken to review our manuscript. > I was not aware of the resemblance to [16] pointed out by reviewer xhDC, which changes my assessment on novelty and therefore less prone to raise the score further. We'd like to address the perceived resemblance between our work and [16] and clarify our contributions, which we partly discussed in the 'Related work' section. While we acknowledge [16] as an inspiring and original contribution to the field, we believe that our work also contributes distinctly and significantly. Similarities: * The use of the neighbor-joining (NJ) algorithm that maps continuous coordinates to a phylogenetic tree * Both works focus on Bayesian phylogenetic inference Differences: * We developed a variational inference (VI) algorithm, while [16] developed an MCMC-based algorithm. * We addressed the issue of parameterizing $Q(\tau)$ in the VI algorithm to cover a vast number of tree topologies, while [16] highlighted the fidelity of hyperbolic spaces to embed the distribution over trees with distances $P(\tau, B_\tau | Y)$. * For the use of the NJ, we explicitly defined a distribution over topologies $Q(\tau) = E_{Q(z)}[I[\tau(z) = \tau]]$ instead of mapping coordinates $z$ to $(\tau, B_\tau)$ as seen in [16]. This distinction is crucial as our approach avoids the issue of the Jacobian determinant seen in [16]. * Unlike [16], our link function $\tau(z)$ does not necessarily rely on NJ, as we don't directly link $z$ to $B_\tau$. We showcase the results using UPGMA in Fig. R3 Fourth. Distinct contributions not comparable to [16]: * We introduced a tractable lower bound $\mathcal{L}$, then explored designs of variational distributions and control variates to complete a novel VI algorithm (GeoPhy). * We benchmarked the model evidence estimations (MLLs) across approaches and exhibited significant improvement over other methods that considered whole topologies. We hope these clarifications address your concerns. > the paper would benefit from mentioning the faster learning runtime of VCSMC and Vaiphy ... Thank you for your suggestion. Accordingly, we will include a discussion on the trade-off of the performance and runtimes between these methods in their standard use in our revised manuscript. > R2 Fourth: I think that the DS1 dataset is not preferable for this analysis, as the support of the MrBayes posterior includes few topologies. > Datasets DS4 and higher would've been a better selection Thank you for the valuable suggestions. In response, we've investigated DS4 and DS7 alongside DS1 to discuss the limitations of $Q(\tau)$, especially in cases with more diffused tree samples. Also, we present the difference of tree topology distributions more clearly by showing (b) the frequency of the most frequent topology and (c) the number of topologies up to their cumulative frequency matches to 95 percentile, in addition to (a) the diversity index. | DS1 | MrBayes | VBPI-GNN | GeoPhy | |--|--:|--:|--:| | (a) Simpson's diversity index | 0.87 | 0.86 | 0.36 | | (b) Top freq. topology | 0.27 | 0.26 | 0.79 | | (c) #topology up to 95% freq. | 42 | 44 | 11 | | DS4 | MrBayes | GeoPhy | |--|--:|--:| | (a) | 0.90 | 0.68 | | (b) | 0.28 | 0.55 | | (c) | 208 | 58 | | DS7 | MrBayes | GeoPhy | |--|--:|--:| | (a) | 0.99 | 0.99 | | (b) | 0.02 | 0.02 | | (c) | 753 | 553 | For DS4, the overall tendencies in GeoPhy: lower (a), higher (b), and lower (c), are observed as DS1. Interestingly, for DS7, we observed that GeoPhy also represents more diverse tree samples than DS1 and DS4. However, the number of unique topologies up to 95% freq. is still lower than MrBayes, which implies the requirement of more expressiveness on $Q(\tau)$ to represent fine topology weights. While the results for VBPI-GNN are not readily available for DS4 and DS7 due to time constraints, we would like to include the corresponding results in our revised manuscript. > Furthermore, what in R2 First-Fourth informs the diversity of the trees sampled by $Q(\tau)$? Given that most tree topologies $\tau$ had very low frequencies, we used the bipartition frequencies of species defined for each tree topology edge as a more concise statistic for the distribution of $Q(\tau)$. In Fig. R2, we present bipartitions ordered by descending frequency as seen in MrBayes. The intermediate values between 0 and 1 in this frequency plot reveal topology diversities, where VBPI-GNN aligns more closely with MrBayes for the DS1 dataset compared to GeoPhy. As GeoPhy tends to take values near zero and one in the slope region, it indicates a need for increased expressiveness of $Q(\tau)$ to better represent intermediate frequencies. This trend was also noticeable for DS4. For DS7, while GeoPhy traced the curve more accurately, fluctuations around this curve highlight potential room for improvement. We intend to incorporate these figures in our updated manuscript.

Authorsrebuttal2023-08-19

Clarifications on Fig. R2 First to Third

We apologize for our oversight of your questions regarding Fig. R2 First to Third. > Q2-1: R2 First to third: I don't understand the experiment behind this, is the consensus trees of Geophy and MrBayes are calculated, and then the ELBO measured under this fixed tree setting? What do each dot represent in each plot? What do 'dim' refer to? Could you please provide a more elaborate description of the experiments behind this plot so I can better assess how they address my concerns. > How many unique trees are used to construct the consensus-tree? We complement the details for Fig. R2 First to Third as follows: Each dot represents a different experimental run. The term 'dim' stands for the dimension of wrapped normal distributions employed for $Q(z)$. We extended our experiments to include 5 and 6 dimensions in response to a query from reviewer AJKq. The procedure is outlined below: 1. We sampled 1000 trees from the posterior distribution $Q(\tau)$ of GeoPhy 2. We then deduced the majority-rule consensus tree from these sampled trees 3. Subsequently, we calculated the Robinson-Foulds (RF) distances between the GeoPhy consensus tree and the consensus tree derived from MrBayes tree samples. Note that the RF metrics are randomly jittered within $\pm 0.2$ to prevent the overlapping of dots in the plot. As the consensus tree is derived from multiple sampled trees, the RF distance represents a summarized metric of alignment of $Q(\tau)$ to MCMC samples. Through Fig. R2 First to Third, we have confirmed that the performance metrics (i.e., MLL estimates) of the GeoPhy model are well aligned with the proximity of $Q(\tau)$ and the MCMC samples in terms of their consensus trees (the modes of the tree topology distribution).

Reviewer Bru62023-08-21

Regarding response to remaining concerns and clarification

Thank you for your extensive investigations regarding my remaining concerns. This, together with the clarifications, addresses all questions I had regarding the submission. The added experiments demonstrate a limitation of the representative power of $Q(\tau)$ of Geophy w.r.t. e.g. VBPI. However, the investigation only makes the paper stronger as it suggests where further improvements of the method can be done. I will raise my score to an 8.

Reviewer MJWZ2023-08-21

I have read through the responses and all of my concerns have been properly addressed. Thus I raised my score to 7.

Program Chairsdecision2023-09-21

Decision

Accept (poster)

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