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Bayzid, M. S.

Publications and source records attributed to Bayzid, M. S..

At least 19 recordsLinked to original sources

Learning Strand-Equivariant Tokenizations of DNA with MirrorDNA

DNA has two strands, and for most regulatory label prediction tasks a sequence and its reverse complement should get same answer. Yet DNA language models are tokenized, trained and tested on one strand at a time. We show that this makes them inconsistent. BPE and $k$-mer tokenizers split 92--100\% of transcription-factor motifs differently on the two strands, and NT-v2, DNABERT-2 and HyenaDNA change 25-31\% of their predictions when the test sequences are reverse-complemented. We introduce {\model}, a compact DNA language model with a learned tokenizer that guarantees mirror-symmetric token boundaries across reverse-complement sequences, regardless of its learned parameters. We prove that this symmetry holds through the whole model. As a result, the same model can give identical answers on both strands when the label does not depend on the strand, and can still tell the strands apart when it does, which no strand-blind model can learn. Counting only predictions that are correct on both strands, \model\ more than doubles the MCC of NT-v2, DNABERT-2 and HyenaDNA. With 2.3M parameters, it is more accurate than the Caduceus models trained on the same data, and not significantly different from NT-v2 (98M parameters) on Genomic Benchmarks or from DNABERT-2 (117M) on the Nucleotide Transformer tasks. It also stays accurate on inputs sixteen times longer than those it was trained on. The same model trained with reverse-complement augmentation instead still changes about one prediction in ten with the strand, unless its outputs are averaged over both strands. Without any annotation, the tokenizer learns to keep the splice-donor signal \texttt{AGGT} in a single token. Code: https://github.com/NIRJHOR-DATTA/MirrorDNA.

bioinformatics↗

QUANTA: A quantum annealing framework for species tree estimation using weighted quartet amalgamation

Reconstructing species trees from genome-scale data is challenging due to pervasive gene tree discordance. Maximizing quartet consistency is a widely used approach for species tree inference from multi-locus data. Quartet amalgamation approaches, such as Quartet Fiduccia-Mattheyse (QFM) and Quartet MaxCut (QMC) families, have emerged as highly accurate quartet-based species tree inference techniques, but their reliance on computationally expensive classical bipartitioning heuristics, such as Fiduccia-Mattheyses (FM) and MaxCut, limits their scalability. Here, we introduce QUANTA, a quantum annealing-based quartet amalgamation method that, to our knowledge, represents the first quantum formulation of quartet-based approaches and the first species tree estimation method for multi-locus data that runs on real quantum hardware. At the core of QUANTA is a novel, general formulation of weighted quartet bipartitioning as a quadratic unconstrained binary optimization (QUBO) problem that enables quantum annealing to replace the classical bipartitioning strategies underlying the QFM and QMC families of methods. We prove that our formulation uses the minimum possible number of qubits to represent bipartitions and that its energy function correctly orders satisfied, deferred, and violated quartets for any positive penalty weights. We implemented QUANTA on real D-Wave quantum annealing hardware, and evaluated it on a wide range of simulated and biological datasets. QUANTA achieves accuracy comparable to the state-of-the-art methods, including ASTRAL and wQFM, under challenging evolutionary conditions. We also reanalyzed several biological datasets, including the avian phylogenomic dataset comprising 14,446 genes across 48 genomes, on which QUANTA reconstructed a species tree with a higher quartet score than wQFM. Remarkably, despite running on current noisy intermediate-scale quantum (NISQ) hardware, QUANTA's bipartition technique achieved 4100x speedup over the FM bipartitioning technique in wQFM on bipartition containing 90-200 taxa, while maintaining comparable tree accuracy. By establishing a theoretically grounded, hardware-independent quantum optimization framework for weighted quartet amalgamation, QUANTA opens a new direction for quantum-assisted phylogenomics and provides a foundation for increasingly scalable and accurate species tree estimation as quantum computing hardware advances. QUANTA is publicly available at https://github.com/QuitttCat/QUANTA-Phylogenomics.

bioinformatics↗

QRAFT: Scaling coalescent-based species tree inference to one million taxa

Species tree inference from multi-locus data under the multispecies coalescent has not kept pace with phylogenomic datasets that now span hundreds of thousands of species. We present QRAFT, a statistically consistent method for estimating species trees by maximizing quartet support on phylogenomic datasets at unprecedented scales. For n taxa and k gene trees, QRAFT achieves near-linear running time of O(kn log^2 n) when its recursion is balanced, which is within a polylogarithmic factor of the O(kn) time required simply to read the input. It also achieves asymptotically optimal O(kn) memory, so its memory requirements grow only linearly with the input size. QRAFT infers a million-taxon species tree from 1,000 genes in just three hours using only 298 GB of RAM, 64 CPU threads, and no GPUs. We estimate that the same analysis with ASTRAL-MP, a scalable parallel implementation of the widely used method ASTRAL, would take about 36 years (>100,000 times longer) and require prohibitive amounts of memory, far beyond practical computational limits. QRAFT maintains accuracy comparable to, and in many cases better than, leading species tree estimation methods. Notably, QRAFT reconstructed a microbial tree of life comprising 199,330 genomes in just a few hours using modest CPU resources. Thus, QRAFT brings highly accurate statistically consistent coalescent-based species tree inference to the unprecedented million-taxon regime and enables phylogenomic analyses towards the scale of the tree of life. QRAFT is publicly available at https://github.com/risenfromashes/qraft.

bioinformatics↗

ASTRAL-X: Scaling Coalescent-Based Species Tree Inference to 300,000 Taxa

Advances in genome sequencing have enabled phylogenomic studies involving tens or even hundreds of thousands of species. However, scalability remains a major computational challenge for statistically consistent species tree inference at this scale. ASTRAL, the most widely used coalescent-based species tree estimator, remains limited by computational and memory bottlenecks that make ultra-large analyses impractical. Here we present ASTRAL-X, a complete algorithmic redesign of the ASTRAL framework that overcomes these computational limitations. By fundamentally redesigning the underlying data representations, algorithms, and computational framework, ASTRAL-X dramatically reduces running time while lowering memory requirements to nearly the size of the input--the asymptotically optimal bound--thereby enabling statistically consistent species tree inference directly from unrooted gene trees at an unprecedented scale. ASTRAL-X preserves ASTRAL's statistical guarantees and achieves accuracy comparable to state-of-the-art methods across simulated and empirical datasets while reconstructing species trees containing 200,000 and 300,000 taxa in only 5 hours and 12 hours, respectively, using modest computational resources. Notably, ASTRAL-X reconstructed the evolutionary history of 9{,}524 angiosperm species in only 16 minutes. These results enable statistically consistent coalescent-based species tree inference at the scale demanded by emerging Tree of Life initiatives. ASTRAL-X is publicly available at \url{https://github.com/aaniksahaa/ASTRAL-X}.

bioinformatics↗

ConnectoFM: A Foundation Model for Learning the Language of the Connectome

Accurate reconstruction of neural circuits from electron microscopy (EM) data is central to connectomics, yet modern datasets are now so large and heterogeneous that manual annotation and dataset-specific model retraining have become major challenges. While recent EM foundation models provide general visual representations, they are not specifically tailored to the connectomics domain, where preserving fine membrane boundaries and synaptic structures is essential to mitigate topological and connectivity errors. Here, we present ConnectoFM, the first foundation model for connectomics, pretrained on a diverse corpus of 1.7 million unlabeled EM images drawn from six species and 25 subdomains. ConnectoFM combines masked image modeling with contrastive alignment to learn robust visual representations directly from large-scale connectomics data. These representations organize EM images into biologically meaningful clusters across species, brain regions, developmental cohorts, and acquisition domains. Using frozen pretrained features with lightweight decoder heads, we transfer ConnectoFM to three important downstream tasks: binary segmentation, multiclass cell typing, and instance segmentation. Across 29 diverse datasets, including established benchmarks, ConnectoFM consistently outperforms existing EM foundation models and state-of-the-art methods that require task-specific training from scratch. With only 10% labeled data, ConnectoFM surpasses the baselines trained on 100% annotation budget, showing the superiority of ConnectoFM in low-data regimes. Improvements of ConnectoFM are especially pronounced for challenging and biologically important targets, including membranes, mitochondria, vesicles, post-synaptic densities and synapses, and remain strong in low-label settings. Extension to 3D volumetric segmentation and qualitative comparisons further show that ConnectoFM enables more accurate and biologically faithful performance across downstream tasks. These results establish ConnectoFM as a generalizable and data-efficient foundation model for connectomics and provide a scalable route towards more reliable neural circuit reconstruction.

neuroscience↗

STEQ: A statistically consistent quartet distance based species tree estimation method

Accurate estimation of large-scale species trees from multilocus data in the presence of gene tree discordance remains a major challenge in phylogenomics. Although maximum likelihood, Bayesian, and statistically consistent summary methods can infer species trees with high accuracy, most of these methods are slow and not scalable to large number of taxa and genes. One of the promising ways for enabling large-scale phylogeny estimation is distance based estimation methods. Here, we present STEQ, a new statistically consistent, fast, and accurate distance based method to estimate species trees from a collection of gene trees. We used a quartet based distance metric which is statistically consistent under the multi-species coalescent (MSC) model. The running time of STEQ scales as [O] (kn2 log n), for n taxa and k genes, which is asymptotically faster than the leading summary based methods such as ASTRAL. We evaluated the performance of STEQ in comparison with ASTRAL and wQFM-TREE - two of the most popular and accurate coalescent-based methods. Experimental findings on a collection of simulated and empirical datasets suggest that STEQ enables significantly faster inference of species trees while maintaining competitive accuracy with the best current methods. STEQ is publicly available at https://github.com/prottoysaha99/STEQ.

bioinformatics↗

Disentangling the Impacts of Incomplete Lineage Sorting and Gene Tree Estimation Error on Species Tree Inference

Accurate species tree inference from genome-scale data is complicated by gene tree discordance, which can arise both from biological processes such as incomplete lineage sorting (ILS) and from technical factors such as gene tree estimation error (GTEE). While both factors reduce the accuracy of summary methods, their relative impact and characteristic patterns remain poorly understood. Here, we systematically compare the effects of ILS and GTEE by simulating gene tree datasets with comparable overall discordance levels, but with discordance arising exclusively from either ILS or GTEE. Using widely employed summary methods such as ASTRAL and wQFM, we show that GTEE typically has a stronger detrimental effect on species tree accuracy than ILS, even at matched discordance levels. We further characterize the structure of gene tree distributions under these two sources of discordance and show that ILS induces a structured, constrained skew in quartet distributions, whereas GTEE generates more uniform, high-entropy noise that does not diminish with additional genes. Our case study on a widely used avian phylogenomic dataset reveals similar distributional patterns across exons, introns, and ultraconserved elements (UCEs), which differ substantially in their levels of phylogenetic signal. A quartet-based analysis of these gene trees further shows that prioritizing loci with stronger and more consistent quartet support can improve the recovery of established avian clades. Overall, these results provide an empirical framework for a nuanced understanding of how ILS and GTEE shape gene tree distributions and influence species tree inference from limited or noisy gene tree datasets.

bioinformatics↗

STELAR-X: Scaling Coalescent-Based Species Tree Inference to 100,000 Species and Beyond

Summary methods reconstruct species trees from collections of gene trees while accounting for gene tree discordance and provide a statistically consistent framework for phylogenomic inference under the multispecies coalescent model. While existing triplet- and quartet-based approaches such as ASTRAL and STELAR have provable statistical consistency, their running time and memory usage restrict their applicability to ultra-large datasets. We introduce STELAR-X, a statistically consistent and highly scalable triplet-based phylogenetic inference algorithm that achieves an asymptotically optimal memory complexity of $O(nk)$ for \textit{n} species and \textit{k} gene trees, essentially matching the input size and allowing analyses to remain feasible as long as the input trees fit in memory, while also substantially reducing running time. STELAR-X achieves this through a compact integer tuple-based encoding of tree bipartitions, efficient precomputation of bipartition weights, and GPU parallelism. These innovations substantially reduce computational overhead in the underlying dynamic programming framework. Experiments demonstrate that STELAR-X achieves unprecedented scalability. On simulated datasets with 10,000 taxa and 1,000 gene trees, STELAR-X runs 3,576$\times$ faster than ASTRAL-MP (the most scalable variant of ASTRAL) while using 13.9$\times$ less CPU memory. STELAR-X analyzed a dataset of 100,000 taxa and 1,000 genes in 34.37 minutes using 58.40 GB RAM, and a 100,000-gene dataset with 1000 taxa in just 3.32 minutes using 74.10 GB RAM, scales that were previously intractable for statistically consistent summary methods. Moreover, applying STELAR-X to two large-scale avian datasets produced trees highly consistent with established bird phylogenies, demonstrating its robustness on biological data.

bioinformatics↗

MExConn: A Mechanistically Interpretable Multi-Expert Framework for Multi-Organelle Segmentation in Connectomics

Electron microscopy (EM) provides subcellular resolution which has made it a critical tool in fields such as cellular biology and connectomics. However, manual annotation of subcellular organelles in these EM images is extremely labor-intensive and impractical at scale. While computational segmentation methods have been developed, most existing approaches are limited to segmenting a single organelle at a time, neglecting the inherent shared information present in EM images containing multiple organelles. To address this, we present MExConn, the first known interpretable multi-expert U-Net architecture in the connectomics field that employs a shared encoder and multiple decoder heads to simultaneously segment multiple organelles from the same input EM image. MExConn significantly outperforms five baselines, including single-organelle model and four state-of-the-art connectomics segmentation models in all evaluation metrics, reducing the Variation of Information by up to 33.54% on average across organelles. A key novelty of our approach is that MExConn offers mechanistic interpretability by revealing that the shared encoder learns shared representations essential for accurately segmenting multiple organelles. Through systematic analysis of encoder gradients with respect to each decoder output, we identify channel-wise importance profiles and reveal that many encoder channels are jointly essential for all organelles, while others are organelle-specific. Rigorous experiments on three connectomics datasets demonstrate the effectiveness of MExConn in both segmentation performance and interpretability, establishing it as a principled approach for multi-organelle analysis in connectomics. The source code is publicly available at https://github.com/abrarrahmanabir/MExConn.

neuroscience↗

MACS: Multi-Domain Adaptation Enables Accurate Connectomics Segmentation

Connectomics aims to map the brains neural wiring by segmenting cellular structures from high-resolution electron microscopy (EM) images. Manual labeling and proofreading remain a major bottleneck for accurate extraction of microstructures. While computational models have advanced automated segmentation, they typically require training from scratch on each dataset, demanding substantial annotated data. Domain adaptation methods address this by transferring knowledge from a labeled source to a less-annotated target. However, existing approaches are limited to adaptation from a single source domain. This overlooks the potential benefits of integrating information from multiple diverse domains, motivating the development of multidomain adaptation. To address this, we propose MACS, the first known multi-domain adaptation framework that combines knowledge from multiple heterogeneous source domains to learn segmentation in the target domain, and employs active learning to efficiently select the most informative target samples for annotation. MACS uses information-theoretic weighting to combine source domains, and introduces a novel and efficient Bayesian Laplace approximation for uncertainty estimation. Our extensive experiments across nine connectomics datasets demonstrate that MACS consistently and substantially outperforms state-of-the-art models, even under limited annotation budgets, with a mean improvement of 5.89% at the lowest annotation budget and 27.72% at the highest annotation budget. In-depth analyses further reveal that MACS offers mechanistic interpretability by quantifying and explicitly upweighting the most transferable source domains for each target. The preprocessed datasets and the source code of MACS are publicly available at http://github.com/abrarrahmanabir/MACS.

neuroscience↗

Quartet-based Genome-scale Species Tree Inference using Multicopy Gene Family Trees

Species tree estimation from multi-copy gene family trees, including both paralogs and orthologs, is a challenging task due to gene tree discordance caused by biological processes such as incomplete lineage sorting (ILS) and gene duplication and loss (GDL). Summary methods, specially quartet-based species tree estimation methods, such as ASTRAL and quartet amalgamation-based methods in the Quartet MaxCut (QMC) and Quartet Fiduccia--Mattheyses (QFM) frameworks, have gained substantial popularity for their accuracy and statistical guarantee. However, most of the summary methods rely on single-copy gene trees and do not explicitly account for GDL, which limits their applicability to large genomic datasets containing multi-copy gene families. ASTRAL-Pro incorporates both orthology and paralogy for species tree inference under GDL by employing a refined quartet similarity measure based on the concept of speciation-driven quartets (SQs). In this study, we propose wQFM-GDL, the first successful initiative to model GDL in a quartet amalgamation-based summary method, using the SQ-based techniques effectively within the QFM framework. This required substantial algorithmic re-engineering, including the development of efficient techniques for computing the initial bipartition in QFM and novel combinatorial methods for computing refined quartet scores directly from gene family trees. In addition, we introduce a locus-aware quartet weight normalization scheme for QFM framework under GDL, which significantly increased the accuracy of our method. We extensively evaluated our method, wQFM-GDL, on benchmark simulated and empirical datasets and compared it with leading methods, including ASTRAL-Pro3, SpeciesRax, FastMulRFS, and DupLoss-2. wQFM-GDL outperforms all other methods in 134 out of 156 model conditions considered in this study, with performance differences becoming more pronounced as dataset size increases. In particular, for larger datasets with 200 and 500 taxa, wQFM-GDL significantly outperforms all the competing methods across all 72 model conditions and achieves, on average, nearly a 25% reduction in reconstruction error compared with ASTRAL-Pro3. wQFM-GDL is freely available in open-source form at https://github.com/abdur-rafi/wQFM-GDL.

evolutionary biology↗

On the robustness to gene tree rooting (or lack thereof) of triplet-based species tree estimation methods

Species tree estimation is frequently based on phylogenomic approaches that use multiple genes from throughout the genome. This process becomes particularly challenging due to gene tree heterogeneity (discordance), often resulting from Incomplete Lineage Sorting (ILS). Triplet and quartet-based approaches for species tree estimation have gained substantial attention as they are provably statistically consistent in the presence of ILS. However, unlike quartet-based methods, the limitation of rooted triplet-based methods in handling unrooted gene trees has restricted their adoption in the systematics community. Furthermore, since the induced triplet distribution in a gene tree depends on the placement of the root, the accuracy of triplet-based methods depends on the accuracy of gene tree rooting. Despite progress in developing methods for rooting unrooted gene trees, greatly understudied is the choice of rooting technique and downstream effects on species tree inference under realistic model conditions. This study involves rigorous empirical testing with different gene tree rooting approaches to establish a nuanced understanding of the impact of rooting on species tree accuracy. Moreover, we aim to investigate the conditions under which triplet-based methods provide more accurate species tree estimations than the widely-used quartet-based methods such as ASTRAL.

evolutionary biology↗

QT-WEAVER: Correcting quartet distribution improves phylogenomic analyses despite gene tree estimation error

Summarizing individual gene trees into species phylogenies using coalescent-based methods has become a standard approach in phylogenomics. However, gene tree estimation error (GTEE) arising from a combination of reasons (ranging from analytical factors to more biological causes, as in short gene sequences) can potentially impact the accuracy of phylogenomic inference. We, for the first time, introduce the problem of correcting the quartet distribution induced by a set of estimated gene trees, which involves updating the weights of the quartets to better reflect their relative importance within the gene tree distribution. We present QT-WEAVER, the first method of its kind, which learns the conflicts within the quartet distribution induced by a given set of gene trees and generates an updated quartet distribution by adjusting the weights accordingly. QT-WEAVER is a general-purpose technique needing no explicit modeling of the subject system or reasons for GTEE or gene tree heterogeneity. Experimental studies on a collection of simulated and empirical data sets suggest that QT-WEAVER can effectively account for GTEE, which results in a substantial improvement in the species tree accuracy. Additionally, the concept of quartet conflicts and related algorithmic and combinatorial innovations introduced in this study will benefit various quartet-based computations. Therefore, QT-WEAVER advances the state-of-the-art in species tree estimation from gene trees in the face of GTEE. QT-WEAVER is freely available in open-source form at https://github.com/navidh86/QT-WEAVER.

bioinformatics↗

BioLLMNet: Enhancing RNA-Interaction Prediction with a Specialized Cross-LLM Transformation Network

Existing computational methods for the prediction of RNA related interactions often rely heavily on manually crafted features. Language model features for bio-sequences has gain significant popularity in proteomics and genomics. However, during interaction prediction, how language model features from different modalities should be combined to extract the most representative features is yet to be explored. We introduce BioLLMNet, a novel framework that introduces an effective combination approach for multi-modal bio-sequences. BioLLMNet provides a way to transform feature space of different molecules language model features and uses learnable gating mechanism to effectively fuse features. Rigorous evaluations show that BioLLMNet achieves state-of-the-art performance in RNA-protein, RNA-small molecule, and RNA-RNA interactions, outperforming existing methods in RNA-associated interaction prediction.

bioinformatics↗

EmbedSimScore: Advancing Protein Similarity Analysis with Structural and Contextual Embeddings

Accurately computing protein similarity is challenging due to the intricate interplay between local substructures and the global structure within protein molecules. Traditional metrics like TM-score often focus on aligning the global structures of the proteins in a rather geometry-based algorithmic way, potentially overlooking critical local-global relations and contextual comparisons. We introduce Embed-SimScore, a novel self-supervised method that generates structural and contextual embeddings by jointly considering both local substructures and global proteins structures. Utilizing contrastive language-structure pre-training (CLSP) and structural contrastive learning, EmbedSimScore captures comprehensive features across different scales of protein structure. These embeddings provide a more precise and holistic means of computing protein similarities, resulting in the identification of intrinsic relations among proteins that traditional approaches overlook.

bioinformatics↗

Leveraging weighted quartet distributions for enhanced species tree inference from genome-wide data

Species tree estimation from genes sampled from throughout the whole genome is challeng-ing in the presence of gene tree discordance, often caused by incomplete lineage sorting (ILS), where alleles can coexist in populations for periods that may span several speciation events. Quartet-based summary methods for estimating species trees from a collection of gene trees are becoming popular due to their high accuracy and theoretical guarantees of robustness to arbitrarily high amounts of ILS. ASTRAL, the most widely used quartet-based method, aims to infer species trees by maximizing the number of quartets in the gene trees that are consistent with the species tree. An alternative approach (as in wQFM) is to infer quartets for all subsets of four species and amalgamate them into a coherent species tree. While summary methods can be highly sensitive to gene tree estimation errors-especially when gene trees are derived from short alignments-quartet amalgamation offers an advantage by potentially bypassing the need for gene tree estimation. However, greatly understudied is the choice of weighted quar-tet inference method and downstream effects on species tree estimations under realistic model conditions. In this study, we investigated a broad range of methods for generating weighted quartets and critically assessed their impact on species tree inference. Our results on a collec-tion of simulated and empirical datasets suggest that amalgamating quartets weighted based on gene tree frequencies (GTF) typically produces more accurate trees than leading quartet-based methods like ASTRAL and SVDquartets. Further enhancements in GTF-based weighted quar-tet estimation were achieved by accounting for gene tree uncertainty, through the utilization of a distribution of trees for each gene (instead of a single tree), by employing traditional nonpara-metric bootstrapping methods or Bayesian MCMC sampling. Our study provides evidence that the careful generation and amalgamation of weighted quartets, as implemented in methods like wQFM, can lead to significantly more accurate trees compared to widely employed methods like ASTRAL, especially in the face of gene tree estimation errors.

bioinformatics↗

wQFM-TREE: highly accurate and scalable quartet-based species tree inference from gene trees

Summary methods are becoming increasingly popular for species tree estimation from multi-locus data in the presence of gene tree discordance. ASTRAL, a leading method in this class, solves the Maximum Quartet Support Species Tree problem within a constrained solution space constructed from the input gene trees. In contrast, alternative heuristics such as wQFM and wQMC operate by taking a set of weighted quartets as input and employ a divide-and-conquer strategy to construct the species tree. Recent studies showed wQFM to be more accurate than ASTRAL and wQMC, though its scalability is hindered by the computational demands of explicitly generating and weighting {Theta}(n4) quartets. Here, we introduce wQFM-TREE, a novel summary method that enhances wQFM by circumventing the need for explicit quartet generation and weighting, thereby enabling its application to large datasets. Unlike wQFM, wQFM-TREE can also handle polytomies. Extensive simulations under diverse and challenging model conditions, with hundreds or thousands of taxa and genes, consistently demonstrate that wQFM-TREE matches or improves upon the accuracy of ASTRAL. Specifically, wQFM-TREE outperformed ASTRAL in 25 of 27 model conditions analyzed in this study involving 200-1000 taxa, with statistically significant differences in 20 of these conditions. Moreover, we applied wQFM-TREE to re-analyze the green plant dataset from the One Thousand Plant Transcriptomes Initiative. Its remarkable accuracy and scalability position wQFM-TREE as a highly competitive alternative to leading methods in the field. Additionally, the algorithmic and combinatorial innovations introduced in this study will benefit various quartet-based computations, advancing the state-of-the-art in phylogenetic estimations.

evolutionary biology↗

BiRNA-BERT Allows Efficient RNA Language Modeling with Adaptive Tokenization

Recent advancements in Transformer-based models have spurred interest in their use for biological sequence analysis. However, adapting models like BERT is challenging due to sequence length, often requiring truncation for proteomics and genomics tasks. Additionally, advanced tokenization and relative positional encoding techniques for long contexts in NLP are often not directly transferable to DNA/RNA sequences, which require nucleotide or character-level encodings for tasks such as 3D torsion angle prediction. To tackle these challenges, we propose an adaptive dual tokenization scheme for bioinformatics that utilizes both nucleotide-level (NUC) and efficient BPE tokenizations. Building on the dual tokenization, we introduce BiRNA-BERT, a 117M parameter Transformer encoder pretrained with our proposed tokenization on 28 billion nucleotides across 36 million coding and non-coding RNA sequences. The learned representation by BiRNA-BERT generalizes across a range of applications and achieves state-of-the-art results in long-sequence downstream tasks and achieves a performance comparable to 6x larger models in short-sequence tasks with 27xless pre-training compute. BiRNA-BERT can dynamically adjust its tokenization strategy based on sequence lengths, utilizing NUC for shorter sequences and switching to BPE for longer ones, thereby offering, for the first time, the capability to efficiently handle arbitrarily long DNA/RNA sequences. 1

bioinformatics↗