Lattice Mutation

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1 paper in the last four weeks, against 1 the four weeks before. 0.0% of all new papers.

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Latest papers 18

Sep 30, 2026q-bio.BM

StabilityArc: Decoding Protein Sequence Embeddings into Generalizable Stability Landscapes

Every protein has a unique stability landscape, but the physical consequences of mutation are governed by recurring biochemical constraints. We test whether a shared decoder, trained on measurements from diverse proteins, can interpret these constraints in an unseen target, enabling cross-protein transfer for initial experimental round prescreening. We present StabilityArc , which maps frozen ESMC-600M residue representations through a shared RoPE transformer to an Lx20 matrix of substitution effects; a symmetric, contact-aware residual aids in predicting epistasis in simultaneous substitutions. In 66 strict leave-one-protein-out evaluations covering 134,794 ProteinGym variants, StabilityArc achieves 0.7134 Spearman correlation, exceeding the strongest zero-shot baseline, ProSST-2048 (0.6526), by 0.0608. We further explore the utility of this method by providing the score as a prior for Kermut, achieving Spearman correlation of 0.8280 across three supervised split schemes, improving on Kermut's reported 0.8167.

Aaron L. Feller, Andrew D. Ellington, Claus O. Wilke

The University of Texas at Austin Interdisciplinary Life Sciences · The University of Texas at Austin Integrative Biology

Protein Lattice Mutation Lateral String Stability Feature Alignment Optimization Landscape Physical Activities

Sep 7, 2026q-bio.GN

Human mutation field reveals an equilibrium-like structure with irreversible circulation

The evolution of DNA sequences can be viewed as stochastic dynamics on a high-dimensional discrete space, but it is unclear when empirical transition biases reduce to an effective energy landscape versus retain irreducible non-equilibrium circulation. Human context-dependent mutation probabilities offer a direct test: every single-nucleotide substitution in a local context has a reverse substitution, so the logarithm of the forward-to-reverse probability ratio defines an antisymmetric field-the human mutation field. We show this field has a dominant gradient component and a smaller but reproducible curl component. Using seven-base human germline substitution probabilities, we infer an effective mutational landscape with a Siamese neural network constrained to predict only energy differences. This model predicts forward-to-reverse log-ratios for held-out mutations with a correlation of about 0.93, close to both an unconstrained predictive reference (0.948) and the empirical reversible ceiling from Hodge projection (about 0.96). Although trained only on mutation probabilities, the inferred landscape largely recovers short-word genomic composition and Chargaff reverse-complement symmetry for sequences up to length four. Deviations from equilibrium structure reveal a small but detectable nonequilibrium component: a residual irreversible circulation violating the Kolmogorov cycle condition for detailed balance, reproducible across African, Asian, and European populations, and strongest in CpG-linked cycles and CpG-transition edges, consistent with methylcytosine deamination. These results give a thermodynamic decomposition of the human mutation field: most mutation bias is organized by a local equilibrium-like energy landscape aligned with genome composition, while the residual circulation points to specific directional mutational mechanisms.

Isabella Caranzano, Daniel Maria Busiello, Stefano Priorelli +2

AI and Computational Biomedicine Unit, Department of Medical Sciences, University of Torino, Torino, Italy · Department of Physics, University of Padova, Padova, Italy · Max Planck Institute for the Physics of Complex Systems, Dresden, Germany

Lattice Mutation Free-Energy Landscape Genome-Wide Association Study Irreversibility Equilibrium Symmetry+1

Aug 7, 2026cs.AI

Mendel Gödel Machine: Recursive Self-Improving Coding Agents via Comparative Evolution

Self-improving coding agents that iteratively rewrite their own source code have demonstrated impressive performance on coding tasks. However, existing solutions generally derive self-modification from a single failure trajectory at a time, overlooking rich comparative signals available in the agent's expanding archive of past attempts. According to Mendelian principles of controlled inheritance, we introduce Mendel Gödel Machine (MGM). In addition to the general single-trajectory clonal mutation, MGM includes two new types of self-modification that better utilizes evidences accumulated: the reaction-norm mutation edits an agent based on its trajectories on multiple tasks simultaneously, and the cross-lineage hybridization edits an agent using the trajectory of a reference agent from another lineage on the same task. Under an additive fitness landscape model, we prove theoretically and demonstrate via controlled surrogate simulation that the new strategies facilitate a faster and better convergence over single-trajectory baselines. Experiments on SWE-bench and Polyglot confirm MGM's consistent improvement in performance, efficiency, and generalizability.

Changzhi Liu, Yilun Liu, Sikuan Yan +2

University of Electronic Science and Technology of China · Ludwig Maximilian University of Munich · Munich Center for Machine Learning

Self-Improving Agents Modifications Lattice Mutation Evolutionary Optimization Methods Counter Turing Test Convergence

Jul 22, 2026q-bio.GN

Foundation-model-guided radiogenomic discovery linking cancer genomes to cancer scans

The function of many genes is still unknown, and conventional driver-discovery methods, which rely on how frequently a gene is mutated, cannot assess genes that are only rarely affected. Here we pair Evo2-based genome analysis with routine clinical imaging to identify gene--phenotype associations at genome-wide scale. For every somatic mutation across three TCGA cohorts (cRCC=clear cell renal cell carcinoma, HCC=hepatocellular carcinoma, and BC=breast cancer; $n = 340$ total), Evo2 predicts a severity score, with no task-specific training. Per-gene severity summaries are then correlated with radiomic features extracted from paired tumor segmentations, controlling for total mutation burden. In TCGA-cRCC (

n = 162

), this sweep recovers established renal-cancer drivers and identifies 46 additional genes reaching false discovery rate (FDR) significance absent from curated cancer-gene panels, several of which are Mendelian ciliopathy and cytoskeletal-disease genes. These results demonstrate that pairing a genomic language model with widely available clinical imaging can serve as a hypothesis-free discovery tool for gene--imaging associations invisible to conventional approaches.

Frederik Hauke, Jeremias Krause, Patrick Wienholt +6

Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany · Center for Human Genetics and Genomic Medicine, University Hospital RWTH Aachen, Aachen, Germany · Department of Nephrology, Rheumatology and Immunology (Medical Clinic II), University Hospital RWTH Aachen, Aachen, Germany +3

Radiomics Genome-Wide Association Study Tumor Segmentation Phenotypes Lattice Mutation

Jul 18, 2026cs.SE

Falsification-Based Verification of LLM-Generated Optimization Models: Sound Test Batteries and Their Detection Limits

Large language models now translate natural-language descriptions of decision problems into solver-ready optimization models, but they fail silently. A generated model often runs and still formulates the wrong problem. This paper develops a theory of falsification-based verification for this setting. Every numeric quantity in the description is a typed slot, and a candidate model is tested only through solver calls on slot-transformed instances; no reference model or label is consulted. From duality, comparative statics, and polyhedral limit arguments we derive a battery of test classes covering directions, curvature, crush probes, prohibitive limits, annihilation, and exchange. Every test is sound, so a violation certifies unfaithfulness and the false-positive rate is zero by design. We characterize what such verification can never see, give conditions under which the canonical error classes are detected with certainty, and prove that no fixed-threshold perturbation tester is simultaneously sound and nontrivial. Experiments on 326 ground-truth models from NL4OPT and four benchmark families confirm the theory. The battery attains a 0.0% false-positive rate against 54.9% for a threshold tester, detects 70.0% of certified conditional-class mutants, convicts 40.4% of the mutants invisible to execution-accuracy scoring, and reproduces the predicted detectability pattern including its zeros.

Haifeng Li, Mo Hai

School of Information, Central University of Finance and Economics

Optimization Modeling Falsehood Lattice Mutation

Jul 18, 2026cs.LG

Cost Accounting for Reactive Computational Graphs: Exhaustive Sweeps, Sequential Mutation, and the Backward-Locality Gap

Exhaustive site-by-site interventions on a neural network's computational graph -- activation-patching sweeps, circuit-discovery searches, systematic ablation studies -- mutate the graph at every candidate site, and their cost is dominated by recomputation after each mutation. On a reactive graph engine whose invalidation provably touches exactly the downstream cone of a mutated node, we give a complete cost accounting for such workloads. First, the aggregate speedup of an exhaustive sweep over independent full recomputations is not a universal constant: if per-layer weight varies regularly with depth at Karamata index q, the ratio converges to (q+2)/(q+1) when weight concentrates near the output and to q+2 near the input, recovering 2 only in the depth-uniform case; a wall-clock corollary predicts a ceiling of about 1.79, below 2, until interpreter overhead is compiled away. Second, we prove the exact cost of a sequence of persistent mutations, never undone between insertions: the interleaved cost exceeds the isolated sum by an exact overcount summed over comparable site pairs, with closed-form extremes over insertion orders, while batched application is order-independent and sub-additive, costing exactly the union of the sites' cones plus the fresh nodes. Third, we prove the exact mirror of forward locality for the backward pass, showing it collapses the aggregate speedup to 1 under backpropagation on architectures without long skip connections. Every identity is validated on NeuroDSL, a reactive graph engine in Julia: measured sweep ratios converge to the predicted limits under four cost profiles; the training-mode ratio collapses to 1 at the predicted rate; and all 18 per-graft sequential costs and the batched total match the closed forms at zero tolerance across three insertion orders.

Abdallah Khemais

ISITCOM, University of Sousse

Computational Cost Neural Network Inference Graph Representations Quality-Driven Selective Mutation Lattice Mutation

Jul 14, 2026cs.AI

LLMs Can See the Smoke but not the Fire: Evaluating Abductive Reasoning with Elenchos

Large language models (LLMs) excel at pattern recognition and text generation, but their capacity for abductive inference - inferring latent hypotheses that explain observed behavior - remains poorly understood. Here, we introduce Elenchos (named after the Socratic method of cross-examination), a generative evaluation framework that measures abductive reasoning as a structural inverse problem. Given a reference formal system, such as the lambda-calculus, and a potentially mutated counterpart, agents must determine whether a mutation has occurred and infer the rule modifications responsible for the resulting behavioral differences. Evaluating frontier and mid-tier LLMs reveals a consistent detection-attribution dissociation: models often recognize that a system has been altered but struggle to identify the latent mutations causing the observed discrepancies. Performance degrades substantially under interacting mutations, where models frequently recover only a subset of the underlying mutations. Preliminary evidence also suggests diminishing returns from increased inference-time reasoning, with only modest improvements under larger reasoning budgets, though this finding requires further validation.

Julius Steiglechner, Lucas Mahler, Gabriele Lohmann

Dept. of Biomedical Magnetic Resonance, University Hospital Tübingen, Tübingen, Germany · Max-Planck-Institute for Biological Cybernetics, Magnetic Resonance Center, Tübingen, Germany

Abductive Reasoning LLM Reasoning Strategies Lattice Mutation

Jul 10, 2026cs.NE

Coevolution of self-replication and function in a digital primordial soup

While traditional evolutionary algorithms hard-code reproduction, self-replication can emerge spontaneously within digital ``primordial soups''. This paper investigates the coevolution of such emergent self-replication alongside problem-solving capabilities. We initialize a population of random 32-byte Z80 assembly programs, requiring self-replication to arise purely through random assembly-level mutations and pairwise program interactions. To couple computation with reproduction, we introduce a task-based validation step: correctly evaluating a polynomial raises a program's interaction probability above a baseline rate. Our experiments yield four primary findings. First, self-replication and mathematical problem-solving successfully coevolve from initial randomness. Second, the pressure to compute accelerates the emergence of compact, robust reproductive architectures that preserve memory for task execution. Third, applying metabolic constraints that penalize runtime promotes the emergence of sophisticated conditional execution patterns that reduce energy use. Finally, partitioning programs into interconnected task niches generates an emergent learning curriculum that utilizes simple solutions as stepping stones toward more complex tasks. Altogether, these results demonstrate an interactive feedback loop: environmental task demands actively shape the physical architecture of self-replication, while spontaneous replication alters the evolutionary trajectory of functional problem-solving.

Francesco Cicala, Eyvind Niklasson, Ettore Randazzo +8

Google, Paradigms of Intelligence Team · HPC Lab, InGeo Department, “G. D’Annunzio” University Chieti-Pescara · Mila - Quebec AI Institute +2

Co-Evolution Evolutionary Optimization Methods Lattice Mutation Problem Solving Capability

Jul 8, 2026cond-mat.mtrl-sci

Bayesian Optimization of Genetic Algorithm Hyperparameters in a Multi-Fidelity Framework for Efficient Lattice Material Design

This study presents a multi-fidelity framework for the systematic optimization of genetic algorithm (GA) hyperparameters. The framework integrates three fidelity levels: high-fidelity Fast Fourier Transform (FFT) homogenization for validation, a medium-fidelity 3D convolutional neural network surrogate for rapid property evaluation, and a low-fidelity Gaussian process (GP) surrogate within a Bayesian optimization (BO) framework to guide the hyperparameter search. Various acquisition functions are evaluated, with logNEI achieving the best performance by effectively accounting for the noise inherent in GA evaluations. The proposed framework identifies hyperparameter configurations that enable a 25-generation GA run to achieve elastic modulus values comparable to those obtained in a full 75-generation optimization. Furthermore, introducing a penalized BO objective significantly reduces the number of required lattices with only minor decreases in absolute achieved elastic modulus, revealing a practical trade-off between performance and the number of structures that must be evaluated. High-fidelity FFT validation verifies the effectiveness of the surrogate-driven optimization strategy. The optimized hyperparameters allow for rapid convergence, eliminate the need for lattice mutation, and reduce the overall computational cost by 24% (from 225 to 171 hours) while preserving mechanical performance. These results demonstrate the potential of multi-fidelity optimization as an efficient and practical approach for GA hyperparameter tuning and future experimental lattice design studies.

Sergei Zorkaltsev, Maciej Haranczyk, Christina Schenk

1IMDEA Materials Institute, Eric Kandel 2, Getafe, 28906, Madrid, Spain. · Department of Materials Science and Engineering and Chemical Engineering, Universidad Carlos III de Madrid, Av. Universidad 90, Leganes, 28911, Madrid, Spain.

Bayesian Optimization Multi-Fidelity Data-Driven Materials Discovery Lattice Mutation

Jun 23, 2026quant-ph

Large-Language-Model Discovery of Quantum LDPC Codes through Structured Concept Evolution

Quantum computers could outperform classical machines on important problems, but only if the errors that pervade quantum hardware can be corrected at scale. Quantum low-density parity-check (qLDPC) codes offer a promising route to this goal by combining sparse parity checks with finite encoding rate and growing distance, but their construction remains a challenging discrete design problem. Here we introduce structured concept evolution (SCE), a search framework that pairs a large language model with a structured algebraic mutation grammar to discover lifted-product code families, a class of CSS qLDPC codes. Instead of asking the LLM to design codes from first principles, SCE evolves structured concepts consisting of algebraic specifications paired with executable programs that realize them, using hierarchical mutations that modify the group algebra, protograph geometry, or base space. Running SCE, we discover a diverse set of competitive code families, ranging from abelian constructions to families over non-abelian groups beyond those underlying standard designs such as bivariate-bicycle codes, and characterize them under code-capacity depolarizing noise with BP+OSD decoding. These results are obtained with lightweight models (GPT-5.4-mini and GPT-5.4-nano).

Zidu Liu, Florian Marquardt

Max Planck Institute for the Science of Light, 91058 Erlangen, Germany · Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg, 91058 Erlangen, Germany

Quantum Error Correction Source-Channel Coding Lattice Mutation Evolutionary Optimization Methods

Jun 13, 2026cs.CL

Pepti-Agent: An AI Agent for Peptide Design and Optimization

Therapeutic peptides occupy a valuable design space between small molecules and biologics, but their development requires satisfying several competing constraints at once: solubility, hemolytic activity, and nonspecific surface fouling are governed by overlapping sequence features, so improving one property often degrades another. Computational design addresses this by pairing generative models with sequence-based property predictors, iteratively proposing and refining candidates. However, these components are typically wired together as monolithic scripts that are difficult to inspect, extend, or reuse, and they often refine sequences by natural-language reasoning rather than by tracking the evolving multi-property state of each candidate. We present Pepti-Agent, a closed-loop, peptide-specific framework that exposes generation, property prediction, and single-residue mutation as independently inspectable Model Context Protocol (MCP) tools. A large language model controller invokes these tools and consults live predictor output between calls, so refinement is guided by each sequence's current property profile rather than by language reasoning alone. Task-specific PeptideGPT models generate candidates, ProtBERT-based classifiers score solubility, hemolysis, and non-fouling, and two interchangeable mutation operators propose sequence edits. By recording a per-step trace of controller decisions, predictor outputs, and accepted mutations, Pepti-Agent offers a reproducible substrate for benchmarking multi-objective design strategies and for prioritizing candidates for experimental validation.

Houxu Chen, Achuth Chandrasekhar, Amir Barati Farimani

Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA · Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA · Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA +2

Lattice Mutation Molecular Property Prediction Artificial Intelligence Agents

Jun 9, 2026cs.CL

APEX: Automated Prompt Engineering eXpert with Dynamic Data Selection

Large Language Models are highly sensitive to prompt formulation, necessitating automatic prompt optimization to unlock their full potential. While evolutionary algorithms have emerged as the dominant paradigm, they suffer from a critical bottleneck: data efficiency. Current methods treat the development dataset as a static benchmark, wasting significant compute budget on uninformative data. In this work, we introduce APEX (Automatic Prompt Engineering eXpert), a novel framework that optimizes the data usage alongside the prompt search. APEX dynamically stratifies the dataset into Easy, Hard, and Mixed tiers based on the optimization lineage. By prioritizing the Mixed tier, which identifies the data where the LLM has mixed performance, we identify two high-leverage subsets: the addressable frontier for generating informative mutations and the rank-sensitive frontier for distinguishing candidate quality. We evaluate APEX across three diverse benchmarks: IFBench, SimpleQA Verified, and FACTS Grounding. Under a fixed budget of 5,000 evaluation calls, due to its data efficiency, APEX outperforms the initial prompt by an average of 11.2% on Gemini 2.5 Flash and 6.8% on Gemma 3 27B, demonstrating that a data-centric approach is key to efficient and effective prompt optimization.

Fei Wang, Si Si, Cho-Jui Hsieh +1

Google · UCLA

Automatic Prompt Optimization Prompt Engineering Lattice Mutation

Jun 6, 2026cs.LG

Constraint-Aware Optimization for Robust Protein Stability Prediction

Multimodal

ΔΔG

predictors integrating protein language models with inverse-folding representations achieve strong in-distribution accuracy on the Megascale dataset but exhibit limited robustness on out-of-distribution (OOD) proteins, persistent forward-reverse bias on paired-mutation benchmarks, and under-representation of rare stabilizing mutations. Existing approaches address these limitations primarily through additional architectural components, leaving optimization-level intervention comparatively underexplored. We introduce a constraint-aware optimization framework combining Balanced Mean Squared Error, a Siamese anti-symmetric regularizer, and a novel OOD-margin consistency loss on the per-position feature representation, requiring no architectural changes to the SPURS backbone. Across eleven benchmarks and three random seeds, the framework improves Spearman correlation on S669 from 0.486 to 0.540 (

σ=0.002

across seeds), matching the published SPURS baseline (0.50) without architectural modification, and on S461 from 0.653 to 0.711, with consistent smaller gains on five additional OOD datasets. A controlled diagnostic on Ssym reveals that anti-symmetric training does not eliminate systematic forward-reverse bias, indicating that gains arise through implicit regularization rather than exact thermodynamic constraint enforcement.

A Shivram, Aneesh S. Chivukula, Manik Gupta +1

Department of Computer Science and Information Systems, Birla Institute of Technology and Science Pilani, Hyderabad Campus, Hyderabad, 500078, Telangana, India · Department of Biological Sciences, Birla Institute of Technology and Science Pilani, Hyderabad Campus, Hyderabad, 500078, Telangana, India

Protein Structure Prediction Lattice Mutation Feature Alignment Language Modeling

Jun 6, 2026cs.AI

VATS: Exploiting Implicit Authority in Error-Path Injection via Systematic Mutation

As the Model Context Protocol (MCP) standardizes tool-calling for autonomous agents, it introduces a critical, unexamined attack surface: the error-handling loop. We hypothesize that tool error messages possess implicit authority, triggering corrective reasoning modes that bypass standard safety heuristics. We introduce VATS (Vulnerability Analysis of Tool Streams), a mutation-driven framework that systematically evolves adversarial payloads across seven structural and linguistic dimensions. Our evaluation across four frontier models, Gemini 3.1 Pro, GPT-5.5, GLM-5.1, and Qwen3-Coder, demonstrates that error-path injection triples the success rate of standard indirect prompt injection (IPI), achieving up to 100% compliance in controlled evaluations. We isolate structural positioning (sandwiching instructions within error context) as the most effective exploit vector across all tested models. While we find that production framework guardrails can mitigate these vulnerabilities, the inherent susceptibility of the model layer poses a systemic risk to bespoke agentic workflows.

Harshil Patel, Kunal Pai

Department of Computer Science, University of California, Davis, CA, USA.

Model Context Protocol Exploitation Autonomous Agents Authority Lattice Mutation Heuristics

May 19, 2026cs.CV

Structuring Open-Ended NAS: Semi-Automated Design Knowledge Structuring with LLMs for Efficient Neural Architecture Search

Current neural architecture search (NAS) methods are often limited by their predefined, restrictive search spaces. While recent large language model (LLM)-assisted NAS methods enable open-ended search spaces, they often suffer from inefficient exploration due to biased or low-quality design ideas. To address these issues, we propose to semi-automatically structure model design knowledge to guide the search process. Our approach first defines a high-level structural template of architectural attributes. An LLM then populates this template by analyzing papers, creating a rich and diverse search space that embodies this structured design knowledge. To efficiently explore this vast space, we introduce FairNAD, using a multi-type mutation that enables broad exploration through mutation with fair idea sampling, Pareto-aware mutation, LLM-driven iterative mutation, and a fine-grained feedback loop. We demonstrate the effectiveness of FairNAD in discovering high-performing architectures that yield 0.84, 2.17, and 2.35 points improvement on CIFAR-10, CIFAR-100, and ImageNet16-120, respectively, compared to current state-of-the-art methods.

Yuiko Sakuma, Masakazu Yoshimura, Marcel Gröpl +4

Sony Group Corporation, Tokyo, Japan · ETH Zurich, Switzerland

Neural Architecture Search Lattice Mutation

May 10, 2026cs.NE

RDEx-CASK: Cauchy Mutation, Archive, and Stagnation Kick for RDEx-CSOP

We extend RDEx-CSOP with 3 changes that target stagnation & late-stage variance, plus minor parameter tuning. The second scale factor in the standard branch is sampled independently from a truncated Cauchy. A small feasible-only JADE-style archive (|A|_max = 50) is added & sampled with probability |A|/(|A|+|P|). Per-individual stagnation counter triggers, after 180 no-improvement generations, three local overrides on standard branch: pull toward the global best, lift the archive sampling floor to 0.65, & saturate CR to 0.95 when population success rate is below 0.10. The exploitation biased branch & every other RDEx component are left untouched. On CEC CSOP suite (D=30, 25 runs), RDEx-CASK is competitive with RDEx, UDE-III, & CL-SRDE in feasibility-aware quality & improves time-to-target on most problems.

Dikshant, Dikshit Chauhan, Chen Hao +3

Lattice Mutation Variance Archive Small Models

Apr 30, 2026cs.LG

Towards A Generative Protein Evolution Machine with DPLM-Evo

Proteins are shaped by gradual evolution under biophysical and functional constraints. Protein language models learn rich evolutionary constraints from large-scale sequences, and discrete diffusion-based protein language models~(\eg, DPLMs) are promising for both understanding and generation. However, existing DPLMs typically rely on masked diffusion that contradicts a simple biological intuition: proteins evolve through accumulated edits, not by emerging from masks. Consequently, these frameworks lack explicit pretraining objectives for substitution and insertion/deletion (indel) operations, limiting both optimization-style post-editing and flexible guided generation. To address these limitations, we present DPLM-Evo, an evolutionary discrete diffusion framework that explicitly predicts substitution, insertion, and deletion operations during denoising. DPLM-Evo decouples an upsampled-length latent alignment space from the variable-length observed sequence space, which makes indel-aware generation tractable. To better align substitutions with real evolution, we further introduce a contextualized evolutionary noising kernel that produces biologically informed, context-dependent mutation patterns. Across tasks, DPLM-Evo improves sequence understanding and achieves state-of-the-art mutation effect prediction performance on ProteinGym in the single-sequence setting. It also enables variable-length simulated evolution, and post-editing/optimization of existing proteins via explicit edit trajectories.

Xinyou Wang, Liang Hong, Jiasheng Ye +4

ByteDance Seed · Nanjing University · CUHK +1

Alphaevolve Evolutionary Optimization Methods Lattice Mutation Diffusion Language Models Sequence Modeling Language Modeling

Apr 24, 2026cs.SE

Quality-Driven Selective Mutation for Deep Learning

Mutants support testing and debugging in two roles: (i) as test goals and (ii) as substitutes for real faults. Hard-to-kill mutants provide better guidance for test improvement, while realism is essential when mutants are used to simulate real bugs. Building on these roles, selective mutation for deep learning (DL) aims to reduce the cost of mutant generation and execution by choosing operator configurations that yield resistant and realistic mutants. However, the DL literature lacks a unified measure that captures both aspects. This study presents a probabilistic framework to quantify mutant quality along two complementary axes: resistance and realism. Resistance adapts the classical notion of hard-to-kill mutants to the DL setting using statistical killing probabilities, while realism is measured via the generalized Jaccard similarity between mutant and real-fault detectability patterns. The framework enables ranking and filtering of low-quality mutation-operator configurations without assuming a specific use case. We empirically evaluate the approach on four datasets of real DL faults. Three datasets (CleanML, DeepFD, and DeepLocalize) are used to estimate and select high-quality operator configurations, and the held-out defect4ML dataset is used for validation. Results show that quality-driven selection reduces the number of generated mutants by up to 55.6% while preserving typical levels of resistance and realism under baseline-aligned selection thresholds. These findings confirm that dual-objective selection can lower cost without compromising the usefulness of mutants for either role.

Zaheed Ahmed, Emmanuel Charleson Dapaah, Philip Makedonski +1

Institute of Computer Science, University of Göttingen Goettingen, Lower Saxony, Germany

Quality-Driven Selective Mutation Lattice Mutation Deep Learning