Daily Papers

We study series-level cinematic remaking, a long-horizon video-to-video generation problem that localizes full episodes or films via stylization or actor replacement while strictly preserving narrative structure, motion choreography, and character identity across hundreds of shots. Existing video generation and editing pipelines often break down in this regime due to compounding identity drift, background mutation, and semantic erosion under large camera motions and viewpoint changes. We propose Soap2Soap, a multi-agent framework that enforces long-term language-visual consistency through a Dual-Bridge Consistency mechanism: a scene-aware JSON screenplay serving as a persistent semantic backbone, and dynamically allocated visual reference anchors at both scene and shot levels. To suppress drift before video synthesis, we introduce batch keyframe consistency, jointly generating multiple keyframes in a shared latent context via a grid-based formulation. A closed-loop verification agent further audits identity, stability, and alignment to trigger selective regeneration. Experiments on SoapBench demonstrate strong improvements over commercial video generation APIs in long-term consistency and narrative fidelity.

The fields of Origin of Life and Artificial Life both question what life is and how it emerges from a distinct set of "pre-life" dynamics. One common feature of most substrates where life emerges is a marked shift in dynamics when self-replication appears. While there are some hypotheses regarding how self-replicators arose in nature, we know very little about the general dynamics, computational principles, and necessary conditions for self-replicators to emerge. This is especially true on "computational substrates" where interactions involve logical, mathematical, or programming rules. In this paper we take a step towards understanding how self-replicators arise by studying several computational substrates based on various simple programming languages and machine instruction sets. We show that when random, non self-replicating programs are placed in an environment lacking any explicit fitness landscape, self-replicators tend to arise. We demonstrate how this occurs due to random interactions and self-modification, and can happen with and without background random mutations. We also show how increasingly complex dynamics continue to emerge following the rise of self-replicators. Finally, we show a counterexample of a minimalistic programming language where self-replicators are possible, but so far have not been observed to arise.

Resonant anomaly detection methods have great potential for enhancing the sensitivity of traditional bump hunt searches. A key component of these methods is a high quality background template used to produce an anomaly score. Using the LHC Olympics R&D dataset, we demonstrate that this background template can also be repurposed to directly estimate the background expectation in a simple cut and count setup. In contrast to a traditional bump hunt, no fit to the invariant mass distribution is needed, thereby avoiding the potential problem of background sculpting. Furthermore, direct background estimation allows working with large background rejection rates, where resonant anomaly detection methods typically show their greatest improvement in significance.

Despite being self-supervised, protein language models have shown remarkable performance in fundamental biological tasks such as predicting impact of genetic variation on protein structure and function. The effectiveness of these models on diverse set of tasks suggests that they learn meaningful representations of fitness landscape that can be useful for downstream clinical applications. Here, we interrogate the use of these language models in characterizing known pathogenic mutations in curated, medically actionable genes through an exhaustive search of putative compensatory mutations on each variant's genetic background. Systematic analysis of the predicted effects of these compensatory mutations reveal unappreciated structural features of proteins that are missed by other structure predictors like AlphaFold. While deep mutational scan experiments provide an unbiased estimate of the mutational landscape, we encourage the community to generate and curate rescue mutation experiments to inform the design of more sophisticated co-masking strategies and leverage large language models more effectively for downstream clinical prediction tasks.

Software testing is a critical, yet resource-intensive phase of the software development lifecycle. Over the years, various automated tools have been developed to aid in this process. Search-based approaches typically achieve high coverage but produce tests with low readability, whereas large language model (LLM)-based methods generate more human-readable tests but often suffer from low coverage and compilability. While the majority of research efforts have focused on improving test coverage and readability, little attention has been paid to enhancing the robustness of bug detection, particularly in exposing corner cases and vulnerable execution paths. To address this gap, we propose AdverTest, a novel adversarial framework for LLM-powered test case generation. AdverTest comprises two interacting agents: a test case generation agent (T) and a mutant generation agent (M). These agents engage in an adversarial loop, where M persistently creates new mutants "hacking" the blind spots of T's current test suite, while T iteratively refines its test cases to "kill" the challenging mutants produced by M. This interaction loop is guided by both coverage and mutation scores, enabling the system to co-evolve toward both high test coverage and bug detection capability. Experimental results in the Defects4J dataset show that our approach improves fault detection rates by 8.56% over the best existing LLM-based methods and by 63.30% over EvoSuite, while also improving line and branch coverage.

During a virus's evolution,various regions of the genome are subjected to distinct levels of functional constraints.Combined with factors like codon bias and DNA repair efficiency,these constraints contribute to unique mutation patterns within the genome or a specific gene. In this project, we harnessed the power of Large Language Models(LLMs) to predict the evolution of SARS-CoV-2. By treating the mutation process from one generation to the next as a translation task, we trained a transformer model, called VirusT5, to capture the mutation patterns underlying SARS-CoV-2 evolution. We evaluated the VirusT5's ability to detect these mutation patterns including its ability to identify mutation hotspots and explored the potential of using VirusT5 to predict future virus variants. Our findings demonstrate the feasibility of using a large language model to model viral evolution as a translation process. This study establishes the groundbreaking concept of "mutation-as-translation," paving the way for new methodologies and tools for combating virus threats

One of the critical phases in software development is software testing. Testing helps with identifying potential bugs and reducing maintenance costs. The goal of automated test generation tools is to ease the development of tests by suggesting efficient bug-revealing tests. Recently, researchers have leveraged Large Language Models (LLMs) of code to generate unit tests. While the code coverage of generated tests was usually assessed, the literature has acknowledged that the coverage is weakly correlated with the efficiency of tests in bug detection. To improve over this limitation, in this paper, we introduce MuTAP for improving the effectiveness of test cases generated by LLMs in terms of revealing bugs by leveraging mutation testing. Our goal is achieved by augmenting prompts with surviving mutants, as those mutants highlight the limitations of test cases in detecting bugs. MuTAP is capable of generating effective test cases in the absence of natural language descriptions of the Program Under Test (PUTs). We employ different LLMs within MuTAP and evaluate their performance on different benchmarks. Our results show that our proposed method is able to detect up to 28% more faulty human-written code snippets. Among these, 17% remained undetected by both the current state-of-the-art fully automated test generation tool (i.e., Pynguin) and zero-shot/few-shot learning approaches on LLMs. Furthermore, MuTAP achieves a Mutation Score (MS) of 93.57% on synthetic buggy code, outperforming all other approaches in our evaluation. Our findings suggest that although LLMs can serve as a useful tool to generate test cases, they require specific post-processing steps to enhance the effectiveness of the generated test cases which may suffer from syntactic or functional errors and may be ineffective in detecting certain types of bugs and testing corner cases PUTs.

To build effective therapeutics, biologists iteratively mutate antibody sequences to improve binding and stability. Proposed mutations can be informed by previous measurements or by learning from large antibody databases to predict only typical antibodies. Unfortunately, the space of typical antibodies is enormous to search, and experiments often fail to find suitable antibodies on a budget. We introduce Clone-informed Bayesian Optimization (CloneBO), a Bayesian optimization procedure that efficiently optimizes antibodies in the lab by teaching a generative model how our immune system optimizes antibodies. Our immune system makes antibodies by iteratively evolving specific portions of their sequences to bind their target strongly and stably, resulting in a set of related, evolving sequences known as a clonal family. We train a large language model, CloneLM, on hundreds of thousands of clonal families and use it to design sequences with mutations that are most likely to optimize an antibody within the human immune system. We propose to guide our designs to fit previous measurements with a twisted sequential Monte Carlo procedure. We show that CloneBO optimizes antibodies substantially more efficiently than previous methods in realistic in silico experiments and designs stronger and more stable binders in in vitro wet lab experiments.

Large language models (LLMs) have shown impressive promise in code generation, yet their progress remains limited by the shortage of large-scale datasets that are both diverse and well-aligned with human reasoning. Most existing resources pair problems with solutions, but omit the intermediate thought process that guides coding. To close this gap, we present a scalable synthetic data generation pipeline that produces nearly 800k instruction-reasoning-code-test quadruplets. Each sample combines a task, a step-by-step reasoning trace, a working solution, and executable tests, enabling models to learn not just the what but also the how of problem solving. Our pipeline combines four key components: curated contest problems, web-mined content filtered by relevance classifiers, data expansion guided by reasoning patterns, and multi-stage execution-based validation. A genetic mutation algorithm further increases task diversity while maintaining consistency between reasoning traces and code implementations. Our key finding is that fine-tuning LLMs on this dataset yields consistent improvements on coding benchmarks. Beyond raw accuracy, reasoning-aware data can substitute for model scaling, generalize across architectures, and outperform leading open-source alternatives under identical sample budgets. Our work establishes reasoning-centered synthetic data generation as an efficient approach for advancing coding capabilities in LLMs. We publish our dataset and generation pipeline to facilitate further research.

A central statistical problem in population genetics is to infer evolutionary and biological parameters such as the strength of natural selection and allele age from DNA samples extracted from a contemporary population. That all samples come only from the present-day has long been known to limit statistical inference; there is potentially more information available if one also has access to ancient DNA so that inference is based on a time-series of historical changes in allele frequencies. We introduce a Markov Chain Monte Carlo (MCMC) method for Bayesian inference from allele frequency time-series data based on an underlying Wright--Fisher diffusion model of evolution, through which one can infer the parameters of essentially any selection model including those with frequency-dependent effects. The chief novelty is that we show this method to be exact in the sense that it is possible to augment the state space explored by MCMC with the unobserved diffusion trajectory, even though the transition function of this diffusion is intractable. Through careful design of a proposal distribution, we describe an efficient method in which updates to the trajectory and accept/reject decisions are calculated without error. We illustrate the method on data capturing changes in coat colour over the past 20,000 years, and find evidence to support previous findings that the mutant alleles ASIP and MC1R responsible for changes in coat color have experienced very strong, possibly overdominant, selection and further provide estimates for the ages of these genes.

Background: Cancer remains one of the leading causes of morbidity and mortality worldwide. Comprehensive datasets that combine histopathological images with genetic and survival data across various tumour sites are essential for advancing computational pathology and personalised medicine. Results: We present SurGen, a dataset comprising 1,020 H&E-stained whole slide images (WSIs) from 843 colorectal cancer cases. The dataset includes detailed annotations for key genetic mutations (KRAS, NRAS, BRAF) and mismatch repair status, as well as survival data for 426 cases. To demonstrate SurGen's practical utility, we conducted a proof-of-concept machine learning experiment predicting mismatch repair status from the WSIs, achieving a test AUROC of 0.8316. These preliminary results underscore the dataset's potential to facilitate research in biomarker discovery, prognostic modelling, and advanced machine learning applications in colorectal cancer. Conclusions: SurGen offers a valuable resource for the scientific community, enabling studies that require high-quality WSIs linked with comprehensive clinical and genetic information on colorectal cancer. Our initial findings affirm the dataset's capacity to advance diagnostic precision and foster the development of personalised treatment strategies in colorectal oncology. Data available online at https://doi.org/10.6019/S-BIAD1285.

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet, a supervised deep-learning model to predict the fitness for protein mutants by leveraging both sequence and structure information, and exploiting attention mechanism. Our model integrates local evolutionary context from homologous sequences, the global evolutionary context encoding rich semantic from the universal protein sequence space and the structure information accounting for the microenvironment around each residue in a protein. We show that SESNet outperforms state-of-the-art models for predicting the sequence-function relationship on 26 deep mutational scanning datasets. More importantly, we propose a data augmentation strategy by leveraging the data from unsupervised models to pre-train our model. After that, our model can achieve strikingly high accuracy in prediction of the fitness of protein mutants, especially for the higher order variants (> 4 mutation sites), when finetuned by using only a small number of experimental mutation data (<50). The strategy proposed is of great practical value as the required experimental effort, i.e., producing a few tens of experimental mutation data on a given protein, is generally affordable by an ordinary biochemical group and can be applied on almost any protein.

It is well known that anti-malware scanners depend on malware signatures to identify malware. However, even minor modifications to malware code structure results in a change in the malware signature thus enabling the variant to evade detection by scanners. Therefore, there exists the need for a proactively generated malware variant dataset to aid detection of such diverse variants by automated antivirus scanners. This paper proposes and demonstrates a generic assembly source code based framework that facilitates any evolutionary algorithm to generate diverse and potential variants of an input malware, while retaining its maliciousness, yet capable of evading antivirus scanners. Generic code transformation functions and a novelty search supported quality metric have been proposed as components of the framework to be used respectively as variation operators and fitness function, for evolutionary algorithms. The results demonstrate the effectiveness of the framework in generating diverse variants and the generated variants have been shown to evade over 98% of popular antivirus scanners. The malware variants evolved by the framework can serve as antigens to assist malware analysis engines to improve their malware detection algorithms.

Common deep learning approaches for antibody engineering focus on modeling the marginal distribution of sequences. By treating sequences as independent samples, however, these methods overlook affinity maturation as a rich and largely untapped source of information about the evolutionary process by which antibodies explore the underlying fitness landscape. In contrast, classical phylogenetic models explicitly represent evolutionary dynamics but lack the expressivity to capture complex epistatic interactions. We bridge this gap with CoSiNE, a continuous-time Markov chain parameterized by a deep neural network. Mathematically, we prove that CoSiNE provides a first-order approximation to the intractable sequential point mutation process, capturing epistatic effects with an error bound that is quadratic in branch length. Empirically, CoSiNE outperforms state-of-the-art language models in zero-shot variant effect prediction by explicitly disentangling selection from context-dependent somatic hypermutation. Finally, we introduce Guided Gillespie, a classifier-guided sampling scheme that steers CoSiNE at inference time, enabling efficient optimization of antibody binding affinity toward specific antigens.

Symbolic regression (SR) is the problem of learning a symbolic expression from numerical data. Recently, deep neural models trained on procedurally-generated synthetic datasets showed competitive performance compared to more classical Genetic Programming (GP) algorithms. Unlike their GP counterparts, these neural approaches are trained to generate expressions from datasets given as context. This allows them to produce accurate expressions in a single forward pass at test time. However, they usually do not benefit from search abilities, which result in low performance compared to GP on out-of-distribution datasets. In this paper, we propose a novel method which provides the best of both worlds, based on a Monte-Carlo Tree Search procedure using a context-aware neural mutation model, which is initially pre-trained to learn promising mutations, and further refined from successful experiences in an online fashion. The approach demonstrates state-of-the-art performance on the well-known SRBench benchmark.

Mutation testing is an effective approach to evaluate and strengthen software test suites, but its adoption is currently limited by the mutants' execution computational cost. Several strategies have been proposed to reduce this cost (a.k.a. mutation cost reduction strategies), however none of them has proven to be effective for all scenarios since they often need an ad-hoc manual selection and configuration depending on the software under test (SUT). In this paper, we propose a novel multi-objective evolutionary hyper-heuristic approach, dubbed Sentinel, to automate the generation of optimal cost reduction strategies for every new SUT. We evaluate Sentinel by carrying out a thorough empirical study involving 40 releases of 10 open-source real-world software systems and both baseline and state-of-the-art strategies as a benchmark. We execute a total of 4,800 experiments, and evaluate their results with both quality indicators and statistical significance tests, following the most recent best practice in the literature. The results show that strategies generated by Sentinel outperform the baseline strategies in 95% of the cases always with large effect sizes. They also obtain statistically significantly better results than state-of-the-art strategies in 88% of the cases, with large effect sizes for 95% of them. Also, our study reveals that the mutation strategies generated by Sentinel for a given software version can be used without any loss in quality for subsequently developed versions in 95% of the cases. These results show that Sentinel is able to automatically generate mutation strategies that reduce mutation testing cost without affecting its testing effectiveness (i.e. mutation score), thus taking off from the tester's shoulders the burden of manually selecting and configuring strategies for each SUT.

This paper describes Meta's ACH system for mutation-guided LLM-based test generation. ACH generates relatively few mutants (aka simulated faults), compared to traditional mutation testing. Instead, it focuses on generating currently undetected faults that are specific to an issue of concern. From these currently uncaught faults, ACH generates tests that can catch them, thereby `killing' the mutants and consequently hardening the platform against regressions. We use privacy concerns to illustrate our approach, but ACH can harden code against {\em any} type of regression. In total, ACH was applied to 10,795 Android Kotlin classes in 7 software platforms deployed by Meta, from which it generated 9,095 mutants and 571 privacy-hardening test cases. ACH also deploys an LLM-based equivalent mutant detection agent that achieves a precision of 0.79 and a recall of 0.47 (rising to 0.95 and 0.96 with simple pre-processing). ACH was used by Messenger and WhatsApp test-a-thons where engineers accepted 73% of its tests, judging 36% to privacy relevant. We conclude that ACH hardens code against specific concerns and that, even when its tests do not directly tackle the specific concern, engineers find them useful for their other benefits.

Fuzzing is an important dynamic program analysis technique designed for finding vulnerabilities in complex software. Fuzzing involves presenting a target program with crafted malicious input to cause crashes, buffer overflows, memory errors, and exceptions. Crafting malicious inputs in an efficient manner is a difficult open problem and the best approaches often apply uniform random mutations to pre-existing valid inputs. In this work, we propose to adopt fine-tuned large language models (FuzzCoder) to learn patterns in the input files from successful attacks to guide future fuzzing explorations. Specifically, we develop a framework to leverage the code LLMs to guide the mutation process of inputs in fuzzing. The mutation process is formulated as the sequence-to-sequence modeling, where LLM receives a sequence of bytes and then outputs the mutated byte sequence. FuzzCoder is fine-tuned on the created instruction dataset (Fuzz-Instruct), where the successful fuzzing history is collected from the heuristic fuzzing tool. FuzzCoder can predict mutation locations and strategies locations in input files to trigger abnormal behaviors of the program. Experimental results show that FuzzCoder based on AFL (American Fuzzy Lop) gain significant improvements in terms of effective proportion of mutation (EPM) and number of crashes (NC) for various input formats including ELF, JPG, MP3, and XML.

In recent years, cancer genome sequencing and other high-throughput studies of cancer genomes have generated many notable discoveries. In this review, Novel genomic alteration mechanisms, such as chromothripsis (chromosomal crisis) and kataegis (mutation storms), and their implications for cancer are discussed. Genomic alterations spur cancer genome evolution. Thus, the relationship between cancer clonal evolution and cancer stems cells is commented. The key question in cancer biology concerns how these genomic alterations support cancer development and metastasis in the context of biological functioning. Thus far, efforts such as pathway analysis have improved the understanding of the functional contributions of genetic mutations and DNA copy number variations to cancer development, progression and metastasis. However, the known pathways correspond to a small fraction, plausibly 5-10%, of somatic mutations and genes with an altered copy number. To develop a comprehensive understanding of the function of these genomic alterations in cancer, an integrative network framework is proposed and discussed. Finally, the challenges and the directions of studying cancer omic data using an integrative network approach are commented.

Evolvability is an important feature that impacts the ability of evolutionary processes to find interesting novel solutions and to deal with changing conditions of the problem to solve. The estimation of evolvability is not straightforward and is generally too expensive to be directly used as selective pressure in the evolutionary process. Indirectly promoting evolvability as a side effect of other easier and faster to compute selection pressures would thus be advantageous. In an unbounded behavior space, it has already been shown that evolvable individuals naturally appear and tend to be selected as they are more likely to invade empty behavior niches. Evolvability is thus a natural byproduct of the search in this context. However, practical agents and environments often impose limits on the reach-able behavior space. How do these boundaries impact evolvability? In this context, can evolvability still be promoted without explicitly rewarding it? We show that Novelty Search implicitly creates a pressure for high evolvability even in bounded behavior spaces, and explore the reasons for such a behavior. More precisely we show that, throughout the search, the dynamic evaluation of novelty rewards individuals which are very mobile in the behavior space, which in turn promotes evolvability.

Many have observed that the development and deployment of generative machine learning (ML) and artificial intelligence (AI) models follow a distinctive pattern in which pre-trained models are adapted and fine-tuned for specific downstream tasks. However, there is limited empirical work that examines the structure of these interactions. This paper analyzes 1.86 million models on Hugging Face, a leading peer production platform for model development. Our study of model family trees -- networks that connect fine-tuned models to their base or parent -- reveals sprawling fine-tuning lineages that vary widely in size and structure. Using an evolutionary biology lens to study ML models, we use model metadata and model cards to measure the genetic similarity and mutation of traits over model families. We find that models tend to exhibit a family resemblance, meaning their genetic markers and traits exhibit more overlap when they belong to the same model family. However, these similarities depart in certain ways from standard models of asexual reproduction, because mutations are fast and directed, such that two `sibling' models tend to exhibit more similarity than parent/child pairs. Further analysis of the directional drifts of these mutations reveals qualitative insights about the open machine learning ecosystem: Licenses counter-intuitively drift from restrictive, commercial licenses towards permissive or copyleft licenses, often in violation of upstream license's terms; models evolve from multi-lingual compatibility towards english-only compatibility; and model cards reduce in length and standardize by turning, more often, to templates and automatically generated text. Overall, this work takes a step toward an empirically grounded understanding of model fine-tuning and suggests that ecological models and methods can yield novel scientific insights.

Nucleotide sequence variation can induce significant shifts in functional fitness. Recent nucleotide foundation models promise to predict such fitness effects directly from sequence, yet heterogeneous datasets and inconsistent preprocessing make it difficult to compare methods fairly across DNA and RNA families. Here we introduce NABench, a large-scale, systematic benchmark for nucleic acid fitness prediction. NABench aggregates 162 high-throughput assays and curates 2.6 million mutated sequences spanning diverse DNA and RNA families, with standardized splits and rich metadata. We show that NABench surpasses prior nucleotide fitness benchmarks in scale, diversity, and data quality. Under a unified evaluation suite, we rigorously assess 29 representative foundation models across zero-shot, few-shot prediction, transfer learning, and supervised settings. The results quantify performance heterogeneity across tasks and nucleic-acid types, demonstrating clear strengths and failure modes for different modeling choices and establishing strong, reproducible baselines. We release NABench to advance nucleic acid modeling, supporting downstream applications in RNA/DNA design, synthetic biology, and biochemistry. Our code is available at https://github.com/mrzzmrzz/NABench.

This paper pursues the insight that large language models (LLMs) trained to generate code can vastly improve the effectiveness of mutation operators applied to programs in genetic programming (GP). Because such LLMs benefit from training data that includes sequential changes and modifications, they can approximate likely changes that humans would make. To highlight the breadth of implications of such evolution through large models (ELM), in the main experiment ELM combined with MAP-Elites generates hundreds of thousands of functional examples of Python programs that output working ambulating robots in the Sodarace domain, which the original LLM had never seen in pre-training. These examples then help to bootstrap training a new conditional language model that can output the right walker for a particular terrain. The ability to bootstrap new models that can output appropriate artifacts for a given context in a domain where zero training data was previously available carries implications for open-endedness, deep learning, and reinforcement learning. These implications are explored here in depth in the hope of inspiring new directions of research now opened up by ELM.

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses and designing novel biotherapeutic proteins. Deep generative models of protein sequences trained on multiple sequence alignments have been the most successful approaches so far to address these tasks. The performance of these methods is however contingent on the availability of sufficiently deep and diverse alignments for reliable training. Their potential scope is thus limited by the fact many protein families are hard, if not impossible, to align. Large language models trained on massive quantities of non-aligned protein sequences from diverse families address these problems and show potential to eventually bridge the performance gap. We introduce Tranception, a novel transformer architecture leveraging autoregressive predictions and retrieval of homologous sequences at inference to achieve state-of-the-art fitness prediction performance. Given its markedly higher performance on multiple mutants, robustness to shallow alignments and ability to score indels, our approach offers significant gain of scope over existing approaches. To enable more rigorous model testing across a broader range of protein families, we develop ProteinGym -- an extensive set of multiplexed assays of variant effects, substantially increasing both the number and diversity of assays compared to existing benchmarks.

This paper presents a reinforced genetic approach to a defined d-resource system optimization problem. The classical evolution schema was ineffective due to a very strict feasibility function in the studied problem. Hence, the presented strategy has introduced several modifications and adaptations to standard genetic routines, e.g.: a migration operator which is an analogy to the biological random genetic drift.

Large language models of code (Code-LLMs) have recently brought tremendous advances to code completion, a fundamental feature of programming assistance and code intelligence. However, most existing works ignore the possible presence of bugs in the code context for generation, which are inevitable in software development. Therefore, we introduce and study the buggy-code completion problem, inspired by the realistic scenario of real-time code suggestion where the code context contains potential bugs -- anti-patterns that can become bugs in the completed program. To systematically study the task, we introduce two datasets: one with synthetic bugs derived from semantics-altering operator changes (buggy-HumanEval) and one with realistic bugs derived from user submissions to coding problems (buggy-FixEval). We find that the presence of potential bugs significantly degrades the generation performance of the high-performing Code-LLMs. For instance, the passing rates of CodeGen-2B-mono on test cases of buggy-HumanEval drop more than 50% given a single potential bug in the context. Finally, we investigate several post-hoc methods for mitigating the adverse effect of potential bugs and find that there remains a large gap in post-mitigation performance.

Antibodies have become an important class of therapeutic agents to treat human diseases. To accelerate therapeutic antibody discovery, computational methods, especially machine learning, have attracted considerable interest for predicting specific interactions between antibody candidates and target antigens such as viruses and bacteria. However, the publicly available datasets in existing works have notable limitations, such as small sizes and the lack of non-binding samples and exact amino acid sequences. To overcome these limitations, we have developed AVIDa-hIL6, a large-scale dataset for predicting antigen-antibody interactions in the variable domain of heavy chain of heavy chain antibodies (VHHs), produced from an alpaca immunized with the human interleukin-6 (IL-6) protein, as antigens. By leveraging the simple structure of VHHs, which facilitates identification of full-length amino acid sequences by DNA sequencing technology, AVIDa-hIL6 contains 573,891 antigen-VHH pairs with amino acid sequences. All the antigen-VHH pairs have reliable labels for binding or non-binding, as generated by a novel labeling method. Furthermore, via introduction of artificial mutations, AVIDa-hIL6 contains 30 different mutants in addition to wild-type IL-6 protein. This characteristic provides opportunities to develop machine learning models for predicting changes in antibody binding by antigen mutations. We report experimental benchmark results on AVIDa-hIL6 by using neural network-based baseline models. The results indicate that the existing models have potential, but further research is needed to generalize them to predict effective antibodies against unknown mutants. The dataset is available at https://avida-hil6.cognanous.com.

During times of increasing antibiotic resistance and the spread of infectious diseases like COVID-19, it is important to classify genes related to antibiotic resistance. As natural language processing has advanced with transformer-based language models, many language models that learn characteristics of nucleotide sequences have also emerged. These models show good performance in classifying various features of nucleotide sequences. When classifying nucleotide sequences, not only the sequence itself, but also various background knowledge is utilized. In this study, we use not only a nucleotide sequence-based language model but also a text language model based on PubMed articles to reflect more biological background knowledge in the model. We propose a method to fine-tune the nucleotide sequence language model and the text language model based on various databases of antibiotic resistance genes. We also propose an LLM-based augmentation technique to supplement the data and an ensemble method to effectively combine the two models. We also propose a benchmark for evaluating the model. Our method achieved better performance than the nucleotide sequence language model in the drug resistance class prediction.

Code execution is a fundamental aspect of programming language semantics that reflects the exact behavior of the code. However, most pre-trained models for code intelligence ignore the execution trace and only rely on source code and syntactic structures. In this paper, we investigate how well pre-trained models can understand and perform code execution. We develop a mutation-based data augmentation technique to create a large-scale and realistic Python dataset and task for code execution, which challenges existing models such as Codex. We then present CodeExecutor, a Transformer model that leverages code execution pre-training and curriculum learning to enhance its semantic comprehension. We evaluate CodeExecutor on code execution and show its promising performance and limitations. We also demonstrate its potential benefits for code intelligence tasks such as zero-shot code-to-code search and text-to-code generation. Our analysis provides insights into the learning and generalization abilities of pre-trained models for code execution.

Discovering mutations enhancing protein-protein interactions (PPIs) is critical for advancing biomedical research and developing improved therapeutics. While machine learning approaches have substantially advanced the field, they often struggle to generalize beyond training data in practical scenarios. The contributions of this work are three-fold. First, we construct PPIRef, the largest and non-redundant dataset of 3D protein-protein interactions, enabling effective large-scale learning. Second, we leverage the PPIRef dataset to pre-train PPIformer, a new SE(3)-equivariant model generalizing across diverse protein-binder variants. We fine-tune PPIformer to predict effects of mutations on protein-protein interactions via a thermodynamically motivated adjustment of the pre-training loss function. Finally, we demonstrate the enhanced generalization of our new PPIformer approach by outperforming other state-of-the-art methods on new, non-leaking splits of standard labeled PPI mutational data and independent case studies optimizing a human antibody against SARS-CoV-2 and increasing the thrombolytic activity of staphylokinase.

Self-evolution methods enhance code generation through iterative "generate-verify-refine" cycles, yet existing approaches suffer from low exploration efficiency, failing to discover solutions with superior complexity within limited budgets. This inefficiency stems from initialization bias trapping evolution in poor solution regions, uncontrolled stochastic operations lacking feedback guidance, and insufficient experience utilization across tasks. To address these bottlenecks, we propose Controlled Self-Evolution (CSE), which consists of three key components. Diversified Planning Initialization generates structurally distinct algorithmic strategies for broad solution space coverage. Genetic Evolution replaces stochastic operations with feedback-guided mechanisms, enabling targeted mutation and compositional crossover. Hierarchical Evolution Memory captures both successful and failed experiences at inter-task and intra-task levels. Experiments on EffiBench-X demonstrate that CSE consistently outperforms all baselines across various LLM backbones. Furthermore, CSE achieves higher efficiency from early generations and maintains continuous improvement throughout evolution. Our code is publicly available at https://github.com/QuantaAlpha/EvoControl.

We introduce a protein language model for determining the complete sequence of a peptide based on measurement of a limited set of amino acids. To date, protein sequencing relies on mass spectrometry, with some novel edman degregation based platforms able to sequence non-native peptides. Current protein sequencing techniques face limitations in accurately identifying all amino acids, hindering comprehensive proteome analysis. Our method simulates partial sequencing data by selectively masking amino acids that are experimentally difficult to identify in protein sequences from the UniRef database. This targeted masking mimics real-world sequencing limitations. We then modify and finetune a ProtBert derived transformer-based model, for a new downstream task predicting these masked residues, providing an approximation of the complete sequence. Evaluating on three bacterial Escherichia species, we achieve per-amino-acid accuracy up to 90.5% when only four amino acids ([KCYM]) are known. Structural assessment using AlphaFold and TM-score validates the biological relevance of our predictions. The model also demonstrates potential for evolutionary analysis through cross-species performance. This integration of simulated experimental constraints with computational predictions offers a promising avenue for enhancing protein sequence analysis, potentially accelerating advancements in proteomics and structural biology by providing a probabilistic reconstruction of the complete protein sequence from limited experimental data.

While the field of Quality-Diversity (QD) has grown into a distinct branch of stochastic optimization, a few problems, in particular locomotion and navigation tasks, have become de facto standards. Are such benchmarks sufficient? Are they representative of the key challenges faced by QD algorithms? Do they provide the ability to focus on one particular challenge by properly disentangling it from others? Do they have much predictive power in terms of scalability and generalization? Existing benchmarks are not standardized, and there is currently no MNIST equivalent for QD. Inspired by recent works on Reinforcement Learning benchmarks, we argue that the identification of challenges faced by QD methods and the development of targeted, challenging, scalable but affordable benchmarks is an important step. As an initial effort, we identify three problems that are challenging in sparse reward settings, and propose associated benchmarks: (1) Behavior metric bias, which can result from the use of metrics that do not match the structure of the behavior space. (2) Behavioral Plateaus, with varying characteristics, such that escaping them would require adaptive QD algorithms and (3) Evolvability Traps, where small variations in genotype result in large behavioral changes. The environments that we propose satisfy the properties listed above.