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q-bio.BM

q-bio.BM: explore 12 source-linked works published from 2026 to 2026, with original documents and citations.

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Includes records with this source-supplied label or an explicit phrase match in their metadata. Matches indicate a mention, not proof that a paper uses a method or tests a material. Source versions are consolidated by DOI.

Sources: arxiv. Collection updated 2026-09-15. Counts describe this index, not the complete source archives.

arXiv2026

Deep Learning-Driven Peptide Classification in Biological Nanopores

Nanopore-based single-molecule sensing is a promising route to fast, low-cost disease diagnosis and protein sequencing: as an analyte such as a peptide or protein traverses a nanoscale pore, it modulates the ionic current, producing a resistive pulse whose signature is determined by the analyte's structure and its interactions with the pore. Translating these signatures into reliable molecular identities, however, is an open problem well suited for machine learning, as the signals are noisy, suffer from variations due to experimental conditions, and are difficult to featurize, which has so far limited classification accuracy. Here we translate the peptide identification problem into an image-classification task by transforming each resistive pulse into a scaleogram via the continuous wavelet transform, a representation that jointly encodes amplitude, frequency, and time in a form well suited for deep convolutional models. On a dataset of 42 peptides, recorded as six separate peptide ladders, this approach reaches a macro-averaged classification accuracy of $82\,\%$ on held-out events, an improvement of $8.6$ percentage points over the descriptor-based approach previously reported for the same dataset. We further show that the trained models tolerate substantial compression, retaining their accuracy with half of their weights set to zero and under 8-bit quantization, a prerequisite for deploying trained classifiers on embedded sensing hardware. Our results demonstrate how physically motivated signal representations can make complex single-molecule data tractable for modern learning algorithms, a step on the path towards point-of-care peptide and protein diagnostics.

cs.LG↗

arXiv2026

SimpleDesign: A Joint Model for Protein Sequence and Structure Codesign

Proteins are fundamental to biological processes, with their function determined by the complex interplay between the amino acid sequence and the three-dimensional structure. Developing generative models capable of understanding this intrinsically multi-modal relationship is crucial for fields like drug discovery and protein engineering. Existing models often rely on a multi-stage training process where autoencoders that tokenize data into latent representations are trained in a first stage. Secondly, a generative model is trained on the latent representation of the autoencoder(s), i.e., generative modeling in a latent space. We hypothesize that this multi-stage training is not necessary to obtain performant co-design models and thus present SimpleDesign, an effective multi-modal protein design model trained directly in the data space. SimpleDesign leverages a single-stage end-to-end objective that combines discrete cross-entropy for sequences and a regression objective for structures. In order to effectively model the difference in sequence and structure modalities, we develop a Mixture-of-Transformer architecture that allows modality-specific processing while keeping global self-attention over both modalities. We train SimpleDesign on over 2M sequence-structure pairs achieving strong performance across co-design and unconditional sequence/structure generation benchmarks.

cs.LG↗

arXiv2026

Advances in Machine Learning for Directed Evolution: A Five-Year Retrospective

The last five-plus years have seen many protein engineering disciplines transformed by advances in machine learning (ML), but the same cannot be said for directed evolution. Reflecting on a previously co-authored perspective, I discuss why I believe this to be the case, arguing that a disconnect between the goals of machine-learning-assisted directed evolution (MLDE) researchers--"identify an optimal protein"--and the goals of directed evolution more broadly--"identify a sufficient protein given time and resource constraints"--is a principal culprit. As an example, I highlight how nearly all current MLDE methods neglect to account for the cost of DNA synthesis, resulting in strategies that have limited practical applicability regardless of the underlying models' capabilities. I close by discussing recent works that are exceptions to this overarching trend, and emphasize that the last five years of efforts in ML-assisted protein engineering and the prescribed reframe of MLDE objectives need not be mutually exclusive.

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arXiv2026

Learning Task-Specific Antibody Representations via Function-Aware Masking

Antibody-specific language models pretrained via masked language modeling (MLM) learn representations that are critical for downstream sequence design and property prediction tasks. Yet, the corruption process itself is rarely leveraged as a source of inductive bias during pretraining. While preferentially masking complementarity-determining regions (CDRs) improves binding-related predictions, antibodies possess diverse biological priors over a variety of functions. Herein, we introduce function-aware masking, a family of pretraining algorithms that align mask placement with specific functional priors (e.g., from IMGT annotations or structure predictions) to shape the learned representation space. We show that these specialist masking strategies significantly improve performance on their respective objectives, yielding up to a 14% gain on structure-related tasks and up to a 5.9x improvement on CDR-related tasks. To further improve performance across multiple functional axes, we develop hybrid masking strategies that integrate multiple priors, balancing reconstruction over binding, structural, and biophysical objectives. Our results demonstrate that informed mask placement provides a parameter-free mechanism for imposing functional inductive biases in antibody language model training.

cs.LG↗

arXiv2026

FLaG: Frequency-Domain Latent-attention Gated Pooling for Token Aggregation

Token aggregation converts token-level representations into fixed-dimensional sample representations, but most pooling methods operate only in the original token space. We introduce Frequency-Domain Latent-attention Gated Pooling (FLaG), a plug-in aggregation module that re-expresses encoder outputs in the Fourier domain before final pooling. FLaG represents the nonredundant rFFT spectrum through concatenated real and imaginary components, summarizes spectral tokens with learnable latent queries, derives a sample-conditioned channel gate, and reconstructs modulated token representations for downstream aggregation. We evaluate the same architecture across ESM2-based antimicrobial peptide (AMP) activity prediction, ResNet18 image classification on CIFAR-10 and CIFAR-100, and three RoBERTa-based language tasks. FLaG achieves the best macro-averaged Spearman correlation coefficient, RMSE, and Recall@50 across four AMP backbone-species settings and the highest top-1 accuracy on CIFAR 10. It also achieves the best mean results on five of seven language metrics, although mean pooling remains strongest on STSBenchmark. AMP-side mechanistic analyses reveal low-frequency prediction sensitivity across most encoder layers, with increased relative high-frequency sensitivity in the final layer, and pronounced peptide-specific positional responses. The residual gate broadly amplifies spectral channels while preserving the low-frequency-dominated energy profile, whereas latent cross-attention exhibits sample- and species-specific spectral allocation. Overall, FLaG provides a transferable frequency-domain aggregation bias across protein, visual, and textual representations, with benefits that depend on the backbone and downstream task. Supplementary materials, source code, and data are available at https://www.healthinformaticslab.org/supp/ and https://github.com/Kewei2023/AMPCliff/tree/FLaG.

cs.AI↗

arXiv2026

CliffRank: A Dual-Branch Framework for Activity-Cliff Ranking Prediction

Activity-cliff ranking remains difficult because local structural changes can cause large activity differences, while high-quality data that resolve the underlying mechanisms remain limited. To use available activity labels more effectively, we combine absolute-activity regression with ranking-consistency learning. CliffRank trains two parallel predictors with mean squared error, a thresholded listwise loss, and Pairwise Preference Consistency (PPC), which aligns relative ordering in the preference-probability space. On three antimicrobial peptide datasets, CliffRank with ESM2-t12 achieved the highest mean Spearman correlation of 0.5393 and mean Recall@50 of 21.4, although the leading method varied across individual datasets. On three small-molecule datasets, CliffRank with PNA, where PPC was activated after 120 epochs, achieved the highest mean Spearman correlation of 0.6890, while its mean Recall@50 of 30.4 matched that of ACANet-PNA. The PPC results also define its practical limits. Asymmetric initialization improved the MolCLR-GIN averages but did not improve every target. For PNA without pretrained weights, delayed PPC improved selected metrics, but no schedule was best for both mean Spearman correlation and mean Recall@50. Future work should evaluate more targets and antimicrobial peptide systems, develop adaptive PPC schedules, and incorporate protein or membrane context when available.

cs.LG↗

arXiv2026

Structural Hierarchy and Geometry in Molecular Representation Learning

Molecular self-supervised learning uses chemical structures to guide which molecular embeddings should be similar. We study whether explicitly encoding a molecule's Bemis-Murcko scaffold and using it to supervise the molecular embedding changes what the model learns. We further test whether this effect depends on the embedding geometry by comparing Euclidean and Lorentz contrastive objectives. Across two augmentation strengths, scaffold-supervised models consistently organize molecules according to both identical and structurally related scaffolds. The resulting embeddings also improve molecular property prediction on several tasks, while the exact gains depend on the predicted property. The effect of scaffold supervision on molecular organization is stronger under Lorentz objectives, but neither geometry provides a consistent overall advantage. These results show that explicitly teaching the relation between a molecule and its structural core can reliably shape the organization of molecular embedding space, while the extent of usefulness of this organization remains task dependent.

cs.LG↗

arXiv2026

Reconstruction-Aware Cryo-EM Particle Picking

Cryo-electron microscopy (cryo-EM) determines the structures of proteins and macromolecular assemblies at near-atomic resolution, and the final 3D reconstruction depends on extracting a clean particle stack from noisy micrographs. This extraction decomposes into three sub-tasks, namely particle picking, contamination removal, and 2D class selection. Each of them, however, is trained and evaluated in isolation, and none is optimized for the reconstruction. We instead integrate the three sub-tasks into a single pipeline posed against downstream reconstruction quality. We instantiate the pipeline with a state-of-the-art component for each sub-task, CryoTransformer picking permissively, MicrographCleaner masking contamination, and CryoSift selecting 2D classes by a continuous quality score, and close the loop with a fine-tuning step that returns the surviving particles to the picker. The pipeline achieves a better 3D resolution than every picker we compare. We also show that the best 2D F1 is not the best resolution, so particle selection is better treated as one reconstruction-aware pipeline judged by the map it delivers.

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arXiv2026

Condition aware learning enables robust prediction of oligonucleotide melting behavior across diverse chemistries and assay conditions

Oligonucleotide melting temperature is a fundamental determinant of nucleic acid hybridization and underpins the design of molecular diagnostics, polymerase chain reaction assays, and many other biotechnology applications. However, accurately predicting melting behavior remains difficult because it depends not only on sequence composition, but also on experimental conditions and chemical modifications commonly used in modern assay design. Existing thermodynamic models rely on fixed parameterizations that are often difficult to extend across diverse reaction environments and nucleotide chemistries. Here we show that a condition-aware nucleotide language model can accurately predict oligonucleotide melting behavior across diverse experimental conditions and both unmodified and chemically modified oligonucleotides. By combining contextual sequence representations with explicit information describing the reaction environment, the framework achieves sub-degree prediction accuracy and reduces prediction error for locked nucleic acid-modified oligonucleotides by up to 25% relative to nearest-neighbor thermodynamic approaches. The model also more accurately captures the thermal effects introduced by nucleotide modification and maintains strong performance on independent benchmark datasets spanning experimental conditions substantially different from those represented during training. Our results demonstrate that learned sequence representations can complement classical thermodynamic models by capturing context-dependent effects that are difficult to encode using fixed parameter tables alone. More broadly, this work provides a scalable framework for predicting oligonucleotide melting behavior across diverse chemistries and assay conditions, supporting more reliable molecular assay design.

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arXiv2026

ZetaDial: dialing net charge of protein binders at inference time for therapeutic developability

Net charge is a developability-relevant property of therapeutic binders, linked to viscosity, clearance, nonspecific interaction and aggregation, and antibody screens already use charge-related criteria. Yet inverse-folding pipelines expose no way to set it to a target value. ProteinMPNN and BindCraft offer amino-acid biases, weight choices and custom losses, but neither supplies a per-protein feedback loop that measures realised charge after sampling and corrects it to a setpoint. ZetaDial contributes a post-sampling, per-protein secant controller around fixed-backbone ProteinMPNN. On matched stochastic benchmarks the secant loop reduced mean absolute error relative to a fixed-slope loop on RCSB complexes (5.17 vs 6.46 charge units) and Cas13 monomers (5.57 vs 8.23). Relative to the optimised matched global bias, it cut RCSB error from 11.71 to 5.17 (cluster bootstrap p < 0.001) and was statistically indistinguishable on Cas13 (5.47 vs 5.57). Across 800 eight-protein subsets, sensitivity heterogeneity was associated with calibration gain (Pearson r = 0.79); this is descriptive resampling, not a prospective decision rule. Foldability deteriorated as bias magnitude increased. In the full 52-complex seed-0 analysis, reference-based DockQ declined clearly at +/-3 but not at +/-1.5; a selected five-seed replication on eight complexes showed paired declines at every nonzero setting, but does not estimate the effect for all 52. In exploratory BindCraft sweeps, PD-L1 designs moved toward near-neutral charge at similar maximum interface pTM but with overlapping success-rate intervals; IL-7R-alpha responses were non-monotonic and RBD produced no strong designs. A fixed-backbone C-alpha-neighbour analysis found smaller same-sign charge-patch proxies near neutral charge, but this proxy is not a measured electrostatic surface or experimental developability endpoint.

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arXiv2026

Novel hybrid protein scaffold gap filling using weighted machine learning ensemble, beam search, and mass-constrained reranking

Protein scaffold gap filling is an important computational task in protein sequence reconstruction, where missing amino acid regions must be inferred from incomplete scaffold information. This study proposes a hybrid machine learning and mass constrained reranking framework for protein scaffold gap filling under known-gap-size and known-gapmass settings. Homologous protein sequences from MabCampath, P5A proteoform, and carbonic anhydrase 2 were used to generate masked 11-mer residue-level samples and fullgap evaluation cases. The residue prediction task was formulated as a 20-class amino acid classification problem using first-, middle-, and last-position masking. Multiple classical machine learning models were trained using raw encoded, row-average, and SVD-reduced features, and the strongest models were combined through a validation-accuracy-weighted ensemble. For known-size gap reconstruction, beam search was used to generate complete missing peptide sequences from residue-level probability estimates. For known-mass reconstruction, mass-constrained homologous candidate retrieval was combined with hybrid reranking based on mass validity, homologous frequency, context support, ensemble likelihood, mass error, and length penalty. The proposed framework achieved 95.41% residue-level validation accuracy, 87.50% known-size exact-match accuracy, and 100% top-5 recovery on seven CAH2 known-mass benchmark cases. These results indicate that the proposed framework can effectively reconstruct missing protein regions by integrating local sequence learning, homologous evidence, peptide mass constraints, and biochemical validation.

q-bio.BM↗

arXiv2026

Symbolic Neural Generation with Applications to Lead Discovery in Drug Design

We investigate a relatively under-explored class of hybrid neurosymbolic models that integrate symbolic learning with neural reasoning to construct data generators meeting formal correctness criteria. In Symbolic Neural Generators (SNGs), symbolic learners examine logical specifications of feasible data from a small set of instances -- sometimes just one. Each specification in turn constrains the conditional information supplied to a neural-based generator, which rejects any instance violating the symbolic specification. Like other neurosymbolic approaches, SNG exploits the complementary strengths of symbolic and neural methods. The outcome of an SNG is a pair $(H, X)$, where $H$ is a symbolic description of feasible instances constructed from data, and $X$ a set of generated new instances that satisfy the description. We introduce a semantics for such systems, based on the construction of appropriate base and fibre partially-ordered sets combined into an overall partial order. We implement an SNG combining a restricted form of Inductive Logic Programming (ILP) with a large language model (LLM) and evaluate it on early-stage drug design. Our main interest is the description and the set of potential inhibitor molecules generated by the SNG. On benchmark problems -- where drug targets are well understood -- SNG performance is statistically comparable to state-of-the-art methods. On exploratory problems with poorly understood targets, generated molecules exhibit binding affinities on par with leading clinical candidates. Experts further find the symbolic specifications useful as preliminary filters, with several generated molecules identified as viable for synthesis and wet-lab testing.

cs.LG↗

Compare source metadata on this page

Work	Published	Source identifier	Source
Deep Learning-Driven Peptide Classification in Biological Nanopores	2026-09-04	2509.14029	arxiv
SimpleDesign: A Joint Model for Protein Sequence and Structure Codesign	2026-09-03	2609.03377	arxiv
Advances in Machine Learning for Directed Evolution: A Five-Year Retrospective	2026-09-02	2609.03046	arxiv
Learning Task-Specific Antibody Representations via Function-Aware Masking	2026-09-01	2609.00518	arxiv
FLaG: Frequency-Domain Latent-attention Gated Pooling for Token Aggregation	2026-09-01	2609.00831	arxiv
CliffRank: A Dual-Branch Framework for Activity-Cliff Ranking Prediction	2026-09-01	2609.01673	arxiv
Structural Hierarchy and Geometry in Molecular Representation Learning	2026-08-30	2608.29886	arxiv
Reconstruction-Aware Cryo-EM Particle Picking	2026-08-28	2608.28838	arxiv
Condition aware learning enables robust prediction of oligonucleotide melting behavior across diverse chemistries and assay conditions	2026-08-05	2609.05454	arxiv
ZetaDial: dialing net charge of protein binders at inference time for therapeutic developability	2026-08-04	2609.05451	arxiv
Novel hybrid protein scaffold gap filling using weighted machine learning ensemble, beam search, and mass-constrained reranking	2026-07-16	2609.05436	arxiv
Symbolic Neural Generation with Applications to Lead Discovery in Drug Design	2026-05-30	2510.23379	arxiv

These are bibliographic comparisons, not experimental rankings. Follow the original document for methods and conditions.