Daily Papers

Phylogenetics is a branch of computational biology that studies the evolutionary relationships among biological entities. Its long history and numerous applications notwithstanding, inference of phylogenetic trees from sequence data remains challenging: the high complexity of tree space poses a significant obstacle for the current combinatorial and probabilistic techniques. In this paper, we adopt the framework of generative flow networks (GFlowNets) to tackle two core problems in phylogenetics: parsimony-based and Bayesian phylogenetic inference. Because GFlowNets are well-suited for sampling complex combinatorial structures, they are a natural choice for exploring and sampling from the multimodal posterior distribution over tree topologies and evolutionary distances. We demonstrate that our amortized posterior sampler, PhyloGFN, produces diverse and high-quality evolutionary hypotheses on real benchmark datasets. PhyloGFN is competitive with prior works in marginal likelihood estimation and achieves a closer fit to the target distribution than state-of-the-art variational inference methods. Our code is available at https://github.com/zmy1116/phylogfn.

Genomic language models (gLMs) have shown mostly modest success in identifying evolutionarily constrained elements in mammalian genomes. To address this issue, we introduce a novel framework for training gLMs that explicitly models nucleotide evolution on phylogenetic trees using multispecies whole-genome alignments. Our approach integrates an alignment into the loss function during training but does not require it for making predictions, thereby enhancing the model's applicability. We applied this framework to train PhyloGPN, a model that excels at predicting functionally disruptive variants from a single sequence alone and demonstrates strong transfer learning capabilities.

Self-supervised representation learning of biological sequence embeddings alleviates computational resource constraints on downstream tasks while circumventing expensive experimental label acquisition. However, existing methods mostly borrow directly from large language models designed for NLP, rather than with bioinformatics philosophies in mind. Recently, contrastive mutual information maximization methods have achieved state-of-the-art representations for ImageNet. In this perspective piece, we discuss how viewing evolution as natural sequence augmentation and maximizing information across phylogenetic "noisy channels" is a biologically and theoretically desirable objective for pretraining encoders. We first provide a review of current contrastive learning literature, then provide an illustrative example where we show that contrastive learning using evolutionary augmentation can be used as a representation learning objective which maximizes the mutual information between biological sequences and their conserved function, and finally outline rationale for this approach.

NeXML is a powerful and extensible exchange standard recently proposed to better meet the expanding needs for phylogenetic data and metadata sharing. Here we present the RNeXML package, which provides users of the R programming language with easy-to-use tools for reading and writing NeXML documents, including rich metadata, in a way that interfaces seamlessly with the extensive library of phylogenetic tools already available in the R ecosystem.

Phylogenetic comparative methods may fail to produce meaningful results when either the underlying model is inappropriate or the data contain insufficient information to inform the inference. The ability to measure the statistical power of these methods has become crucial to ensure that data quantity keeps pace with growing model complexity. Through simulations, we show that commonly applied model choice methods based on information criteria can have remarkably high error rates; this can be a problem because methods to estimate the uncertainty or power are not widely known or applied. Furthermore, the power of comparative methods can depend significantly on the structure of the data. We describe a Monte Carlo based method which addresses both of these challenges, and show how this approach both quantifies and substantially reduces errors relative to information criteria. The method also produces meaningful confidence intervals for model parameters. We illustrate how the power to distinguish different models, such as varying levels of selection, varies both with number of taxa and structure of the phylogeny. We provide an open-source implementation in the pmc ("Phylogenetic Monte Carlo") package for the R programming language. We hope such power analysis becomes a routine part of model comparison in comparative methods.

Multilingual language models have pushed state-of-the-art in cross-lingual NLP transfer. The majority of zero-shot cross-lingual transfer, however, use one and the same massively multilingual transformer (e.g., mBERT or XLM-R) to transfer to all target languages, irrespective of their typological, etymological, and phylogenetic relations to other languages. In particular, readily available data and models of resource-rich sibling languages are often ignored. In this work, we empirically show, in a case study for Faroese -- a low-resource language from a high-resource language family -- that by leveraging the phylogenetic information and departing from the 'one-size-fits-all' paradigm, one can improve cross-lingual transfer to low-resource languages. In particular, we leverage abundant resources of other Scandinavian languages (i.e., Danish, Norwegian, Swedish, and Icelandic) for the benefit of Faroese. Our evaluation results show that we can substantially improve the transfer performance to Faroese by exploiting data and models of closely-related high-resource languages. Further, we release a new web corpus of Faroese and Faroese datasets for named entity recognition (NER), semantic text similarity (STS), and new language models trained on all Scandinavian languages.

This paper introduces PhyloLM, a method adapting phylogenetic algorithms to Large Language Models (LLMs) to explore whether and how they relate to each other and to predict their performance characteristics. Our method calculates a phylogenetic distance metrics based on the similarity of LLMs' output. The resulting metric is then used to construct dendrograms, which satisfactorily capture known relationships across a set of 111 open-source and 45 closed models. Furthermore, our phylogenetic distance predicts performance in standard benchmarks, thus demonstrating its functional validity and paving the way for a time and cost-effective estimation of LLM capabilities. To sum up, by translating population genetic concepts to machine learning, we propose and validate a tool to evaluate LLM development, relationships and capabilities, even in the absence of transparent training information.

Motivation The genotype assignment problem consists of predicting, from the genotype of an individual, which of a known set of populations it originated from. The problem arises in a variety of contexts, including wildlife forensics, invasive species detection and biodiversity monitoring. Existing approaches perform well under ideal conditions but are sensitive to a variety of common violations of the assumptions they rely on. Results In this article, we introduce Mycorrhiza, a machine learning approach for the genotype assignment problem. Our algorithm makes use of phylogenetic networks to engineer features that encode the evolutionary relationships among samples. Those features are then used as input to a Random Forests classifier. The classification accuracy was assessed on multiple published empirical SNP, microsatellite or consensus sequence datasets with wide ranges of size, geographical distribution and population structure and on simulated datasets. It compared favorably against widely used assessment tests or mixture analysis methods such as STRUCTURE and Admixture, and against another machine-learning based approach using principal component analysis for dimensionality reduction. Mycorrhiza yields particularly significant gains on datasets with a large average fixation index (FST) or deviation from the Hardy-Weinberg equilibrium. Moreover, the phylogenetic network approach estimates mixture proportions with good accuracy.

A central problem in biology is to understand how organisms evolve and adapt to their environment by acquiring variations in the observable characteristics or traits of species across the tree of life. With the growing availability of large-scale image repositories in biology and recent advances in generative modeling, there is an opportunity to accelerate the discovery of evolutionary traits automatically from images. Toward this goal, we introduce Phylo-Diffusion, a novel framework for conditioning diffusion models with phylogenetic knowledge represented in the form of HIERarchical Embeddings (HIER-Embeds). We also propose two new experiments for perturbing the embedding space of Phylo-Diffusion: trait masking and trait swapping, inspired by counterpart experiments of gene knockout and gene editing/swapping. Our work represents a novel methodological advance in generative modeling to structure the embedding space of diffusion models using tree-based knowledge. Our work also opens a new chapter of research in evolutionary biology by using generative models to visualize evolutionary changes directly from images. We empirically demonstrate the usefulness of Phylo-Diffusion in capturing meaningful trait variations for fishes and birds, revealing novel insights about the biological mechanisms of their evolution.

Natural selection for terrestrial locomotion has yielded unifying patterns in the body shape of legged animals, often manifesting as scaling laws. One such pattern appears in the frontal aspect ratio. Smaller animals like insects typically adopt a landscape frontal aspect ratio, with a wider side-to-side base of support than center of mass height. Larger animals like elephants, however, are taller than wide with a portrait aspect ratio. Known explanations for postural scaling are restricted to animal groups with similar anatomical and behavioural motifs, but the trend in frontal aspect ratio transcends such commonalities. Here we show that vertebrates and invertebrates with diverse body plans, ranging in mass from 28 mg to 22000 kg, exhibit size-dependent scaling of the frontal aspect ratio driven by the need for lateral stability on uneven natural terrain. Because natural terrain exhibit scale-dependent unevenness, and the frontal aspect ratio is important for lateral stability during locomotion, smaller animals need a wider aspect ratio for stability. This prediction is based on the fractal property of natural terrain unevenness, requires no anatomical or behavioural parameters, and agrees with the measured scaling despite vast anatomical and behavioural differences. Furthermore, a statistical phylogenetic comparative analysis found that shared ancestry and random trait evolution cannot explain the measured scaling. Thus, our findings reveal that terrain roughness, acting through natural selection for stability, likely drove the macroevolution of frontal shape in terrestrial animals.

We introduce EvoGit, a decentralized multi-agent framework for collaborative software development driven by autonomous code evolution. EvoGit deploys a population of independent coding agents, each proposing edits to a shared codebase without centralized coordination, explicit message passing, or shared memory. Instead, all coordination emerges through a Git-based phylogenetic graph that tracks the full version lineage and enables agents to asynchronously read from and write to the evolving code repository. This graph-based structure supports fine-grained branching, implicit concurrency, and scalable agent interaction while preserving a consistent historical record. Human involvement is minimal but strategic: users define high-level goals, periodically review the graph, and provide lightweight feedback to promote promising directions or prune unproductive ones. Experiments demonstrate EvoGit's ability to autonomously produce functional and modular software artifacts across two real-world tasks: (1) building a web application from scratch using modern frameworks, and (2) constructing a meta-level system that evolves its own language-model-guided solver for the bin-packing optimization problem. Our results underscore EvoGit's potential to establish a new paradigm for decentralized, automated, and continual software development. EvoGit is open-sourced at https://github.com/BillHuang2001/evogit.

Discovering evolutionary traits that are heritable across species on the tree of life (also referred to as a phylogenetic tree) is of great interest to biologists to understand how organisms diversify and evolve. However, the measurement of traits is often a subjective and labor-intensive process, making trait discovery a highly label-scarce problem. We present a novel approach for discovering evolutionary traits directly from images without relying on trait labels. Our proposed approach, Phylo-NN, encodes the image of an organism into a sequence of quantized feature vectors -- or codes -- where different segments of the sequence capture evolutionary signals at varying ancestry levels in the phylogeny. We demonstrate the effectiveness of our approach in producing biologically meaningful results in a number of downstream tasks including species image generation and species-to-species image translation, using fish species as a target example.

This paper presents LOLA, a massively multilingual large language model trained on more than 160 languages using a sparse Mixture-of-Experts Transformer architecture. Our architectural and implementation choices address the challenge of harnessing linguistic diversity while maintaining efficiency and avoiding the common pitfalls of multilinguality. Our analysis of the evaluation results shows competitive performance in natural language generation and understanding tasks. Additionally, we demonstrate how the learned expert-routing mechanism exploits implicit phylogenetic linguistic patterns to potentially alleviate the curse of multilinguality. We provide an in-depth look at the training process, an analysis of the datasets, and a balanced exploration of the model's strengths and limitations. As an open-source model, LOLA promotes reproducibility and serves as a robust foundation for future research. Our findings enable the development of compute-efficient multilingual models with strong, scalable performance across languages.

Accurate computational identification of DNA methylation is essential for understanding epigenetic regulation. Although deep learning excels in this binary classification task, its "black-box" nature impedes biological insight. We address this by introducing a high-performance model MEDNA-DFM, alongside mechanism-inspired signal purification algorithms. Our investigation demonstrates that MEDNA-DFM effectively captures conserved methylation patterns, achieving robust distinction across diverse species. Validation on external independent datasets confirms that the model's generalization is driven by conserved intrinsic motifs (e.g., GC content) rather than phylogenetic proximity. Furthermore, applying our developed algorithms extracted motifs with significantly higher reliability than prior studies. Finally, empirical evidence from a Drosophila 6mA case study prompted us to propose a "sequence-structure synergy" hypothesis, suggesting that the GAGG core motif and an upstream A-tract element function cooperatively. We further validated this hypothesis via in silico mutagenesis, confirming that the ablation of either or both elements significantly degrades the model's recognition capabilities. This work provides a powerful tool for methylation prediction and demonstrates how explainable deep learning can drive both methodological innovation and the generation of biological hypotheses.

In this paper, we present gfnx, a fast and scalable package for training and evaluating Generative Flow Networks (GFlowNets) written in JAX. gfnx provides an extensive set of environments and metrics for benchmarking, accompanied with single-file implementations of core objectives for training GFlowNets. We include synthetic hypergrids, multiple sequence generation environments with various editing regimes and particular reward designs for molecular generation, phylogenetic tree construction, Bayesian structure learning, and sampling from the Ising model energy. Across different tasks, gfnx achieves significant wall-clock speedups compared to Pytorch-based benchmarks (such as torchgfn library) and author implementations. For example, gfnx achieves up to 55 times speedup on CPU-based sequence generation environments, and up to 80 times speedup with the GPU-based Bayesian network structure learning setup. Our package provides a diverse set of benchmarks and aims to standardize empirical evaluation and accelerate research and applications of GFlowNets. The library is available on GitHub (https://github.com/d-tiapkin/gfnx) and on pypi (https://pypi.org/project/gfnx/). Documentation is available on https://gfnx.readthedocs.io.

Since its emergence, SARS-CoV-2 has demonstrated a rapid and unpredictable evolutionary trajectory, characterized by the continual emergence of immune-evasive variants. This poses persistent challenges to public health and vaccine development. While large-scale generative pre-trained transformers (GPTs) have revolutionized the modeling of sequential data, their direct applications to noisy viral genomic sequences are limited. In this paper, we introduce PETRA(Pretrained Evolutionary TRAnsformer), a novel transformer approach based on evolutionary trajectories derived from phylogenetic trees rather than raw RNA sequences. This method effectively mitigates sequencing noise and captures the hierarchical structure of viral evolution. With a weighted training framework to address substantial geographical and temporal imbalances in global sequence data, PETRA excels in predicting future SARS-CoV-2 mutations, achieving a weighted recall@1 of 9.45% for nucleotide mutations and 17.10\% for spike amino-acid mutations, compared to 0.49% and 6.64% respectively for the best baseline. PETRA also demonstrates its ability to aid in the real-time mutation prediction of major clades like 24F(XEC) and 25A(LP.8.1). The code is open sourced on https://github.com/xz-keg/PETra

Pretrained language models (PLMs) have shown remarkable generalization toward multiple tasks and languages. Nonetheless, the generalization of PLMs towards unseen languages is poor, resulting in significantly worse language performance, or even generating nonsensical responses that are comparable to a random baseline. This limitation has been a longstanding problem of PLMs raising the problem of diversity and equal access to language modeling technology. In this work, we solve this limitation by introducing LinguAlchemy, a regularization technique that incorporates various aspects of languages covering typological, geographical, and phylogenetic constraining the resulting representation of PLMs to better characterize the corresponding linguistics constraints. LinguAlchemy significantly improves the accuracy performance of mBERT and XLM-R on unseen languages by ~18% and ~2%, respectively compared to fully finetuned models and displaying a high degree of unseen language generalization. We further introduce AlchemyScale and AlchemyTune, extension of LinguAlchemy which adjusts the linguistic regularization weights automatically, alleviating the need for hyperparameter search. LinguAlchemy enables better cross-lingual generalization to unseen languages which is vital for better inclusivity and accessibility of PLMs.

Polyploidization is an important evolutionary process which affects organisms ranging from plants to fish and fungi. The signal left behind by it is in the form of a species' ploidy level (number of complete chromosome sets found in a cell) which is inherently non-treelike. Currently available tools for reconstructing the evolutionary past of a polyploid dataset generally start with a multi-labelled tree obtained for a dataset of interest and then derive a (phylogenetic) network from that tree in some way that reflects that past by interpreting the networks's vertices of indegree at least two as polyploidization events. Since obtaining such a tree can be computationally expensive it is paramount to have alternative approaches available that allow one to shed light into the reticulate evolutionary past of a polyploid dataset. SPRINT aims to reconstruct the evolutionary past of a polyploid dataset in terms of a binary network which realises the dataset's ploidy profile (vector of ploidy levels of the dataset's taxa) and requires the fewest number of polyploidization events. It does this by representing the ploidy level of a species x in terms of the number of directed paths from the root of the network to the leaf of the network labelled by x. SPRINT is distributed on GitHub: https://github.com/lmaher1/SPRINT.

We develop information geometric techniques to understand the representations learned by deep networks when they are trained on different tasks using supervised, meta-, semi-supervised and contrastive learning. We shed light on the following phenomena that relate to the structure of the space of tasks: (1) the manifold of probabilistic models trained on different tasks using different representation learning methods is effectively low-dimensional; (2) supervised learning on one task results in a surprising amount of progress even on seemingly dissimilar tasks; progress on other tasks is larger if the training task has diverse classes; (3) the structure of the space of tasks indicated by our analysis is consistent with parts of the Wordnet phylogenetic tree; (4) episodic meta-learning algorithms and supervised learning traverse different trajectories during training but they fit similar models eventually; (5) contrastive and semi-supervised learning methods traverse trajectories similar to those of supervised learning. We use classification tasks constructed from the CIFAR-10 and Imagenet datasets to study these phenomena.