Reinforcement Learning from Human Feedback (RLHF) is essential for aligning large language models (LLMs) with human preferences and values. While recent research has primarily focused on algorithmic advancements--such as reducing computational overhead or strengthening reward models to mitigate reward hacking--the critical role of prompt-data construction and its scalability has received comparatively less attention. In this paper, we address this gap by systematically exploring data-driven bottlenecks that currently hinder RLHF performance scaling, focusing specifically on the challenges posed by reward hacking and decreasing response diversity. To mitigate reward hacking, we introduce a hybrid reward system combining reasoning task verifiers (RTV) and a generative reward model (GenRM). This approach enables accurate assessment of responses against clearly defined ground-truth solutions. Additionally, in order to ensure response diversity and enhance learning effectiveness, we propose a novel prompt-selection method named Pre-PPO, explicitly identifying training prompts that are inherently challenging and thus less prone to reward hacking.

Predicting disease risk from DNA presents an unprecedented emerging challenge as biobanks approach population scale sizes (N > 106 individuals) with ultra-highdimensional features (L > 105 genotypes). Current methods, often linear and reliant on summary statistics, fail to capture complex genetic interactions and discard valuable individual-level information. We introduce PRSformer, a scalable deep learning architecture designed for end-to-end, multitask disease prediction directly from million-scale individual genotypes. PRSformer employs neighborhood attention, achieving linear O(L) complexity per layer, making Transformers tractable for genome-scale inputs. Crucially, PRSformer utilizes a stacking of these efficient attention layers, progressively increasing the effective receptive field to model local dependencies (e.g., within linkage disequilibrium blocks) before integrating information across wider genomic regions. This design, tailored for genomics, allows PRSformer to learn complex, potentially non-linear and long-range interactions directly from raw genotypes. We demonstrate PRSformer's effectiveness using a unique large private cohort (N 5M) for predicting 18 autoimmune and inflammatory conditions using L 140k variants. PRSformer significantly outperforms highly optimized linear models trained on the same individual-level data and state-of-the-art summary-statistic-based methods (LDPred2) derived from the same cohort, quantifying the benefits of non-linear modeling and multitask learning at scale. Furthermore, experiments reveal that the advantage of non-linearity emerges primarily at large sample sizes (N > 1M), and that a multi-ancestry trained model improves generalization, establishing PRSformer as a new framework for deep learning in population-scale genomics.

Predicting disease risk from DNA presents an unprecedented emerging challenge as biobanks approach population scale sizes ($N> 10^6$ individuals) with ultra-high-dimensional features ($L> 10^5$ genotypes). Current methods, often linear and reliant on summary statistics, fail to capture complex genetic interactions and discard valuable individual-level information. We introduce **PRSformer**, a scalable deep learning architecture designed for end-to-end, multitask disease prediction directly from million-scale individual genotypes. PRSformer employs neighborhood attention, achieving linear $O(L)$ complexity per layer, making Transformers tractable for genome-scale inputs. Crucially, PRSformer utilizes a stacking of these efficient attention layers, progressively increasing the effective receptive field to model local dependencies (e.g., within linkage disequilibrium blocks) before integrating information across wider genomic regions. This design, tailored for genomics, allows PRSformer to learn complex, potentially non-linear and long-range interactions directly from raw genotypes. We demonstrate PRSformer's effectiveness using a unique large private cohort ($N \approx 5$M) for predicting 18 autoimmune and inflammatory conditions using $L \approx 140$k variants. PRSformer significantly outperforms highly optimized linear models trained on the *same individual-level data* and state-of-the-art summary-statistic-based methods (LDPred2) derived from the *same cohort*, quantifying the benefits of non-linear modeling and multitask learning at scale. Furthermore, experiments reveal that the advantage of non-linearity emerges primarily at large sample sizes ($N > 1$M), and that a multi-ancestry trained model improves generalization, establishing PRSformer as a new framework for deep learning in population-scale genomics.

Recently, Neural Architecture Search has achieved great success in large-scale imageclassification.

Neural Information Processing Systems http://nips.cc/

This is the accepted version of the paper published in Journal of Theoretical & Applied Information Technology Vol 4 No 8 (2008) . ABSTRACT 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. INTRODUCTION A funda mental goal in computer science is to provide an algorithm which would determine an optimal solution in acceptable time. Computational Complexity Theory is the field which studies the efficiency of computation; its major goals are to find efficient algorit hms for natural problems or to show that no efficient solutions exist. NP - hard (Nondeterministic Polynomial - time hard), represents a class of problems which are'at least as difficult as problems in NP' [7] [19] . NP - complete problems can be solve d by means of exhaustive search.

Machine learning models increasingly map biological sequence-fitness landscapes to predict mutational effects. Effective evaluation of these models requires benchmarks curated from empirical data. Despite their impressive scales, existing benchmarks lack topographical information regarding the underlying fitness landscapes, which hampers interpretation and comparison of model performance beyond averaged scores. Here, we introduce GraphFLA, a Python framework that constructs and analyzes fitness landscapes from mutagensis data in diverse modalities (e.g., DNA, RNA, protein, and beyond) with up to millions of mutants. GraphFLA calculates 20 biologically relevant features that characterize 4 fundamental aspects of landscape topography. By applying GraphFLA to over 5,300 landscapes from ProteinGym, RNAGym, and CIS-BP, we demonstrate its utility in interpreting and comparing the performance of dozens of fitness prediction models, highlighting factors influencing model accuracy and respective advantages of different models. In addition, we release 155 combinatorially complete empirical fitness landscapes, encompassing over 2.2 million sequences across various modalities. All the codes and datasets are available at https://github.com/COLA-Laboratory/GraphFLA.

We extend biologically-informed neural networks (BINNs) for genomic prediction (GP) and selection (GS) in crops by integrating thousands of single-nucleotide polymorphisms (SNPs) with multi-omics measurements and prior biological knowledge. Traditional genotype-to-phenotype (G2P) models depend heavily on direct mappings that achieve only modest accuracy, forcing breeders to conduct large, costly field trials to maintain or marginally improve genetic gain. Models that incorporate intermediate molecular phenotypes such as gene expression can achieve higher predictive fit, but they remain impractical for GS since such data are unavailable at deployment or design time. BINNs overcome this limitation by encoding pathway-level inductive biases and leveraging multi-omics data only during training, while using genotype data alone during inference. Applied to maize gene-expression and multi-environment field-trial data, BINN improves rank-correlation accuracy by up to 56% within and across subpopulations under sparse-data conditions and nonlinearly identifies genes that GWAS/TWAS fail to uncover. With complete domain knowledge for a synthetic metabolomics benchmark, BINN reduces prediction error by 75% relative to conventional neural nets and correctly identifies the most important nonlinear pathway. Importantly, both cases show highly sensitive BINN latent variables correlate with the experimental quantities they represent, despite not being trained on them. This suggests BINNs learn biologically-relevant representations, nonlinear or linear, from genotype to phenotype. Together, BINNs establish a framework that leverages intermediate domain information to improve genomic prediction accuracy and reveal nonlinear biological relationships that can guide genomic selection, candidate gene selection, pathway enrichment, and gene-editing prioritization.

The competitive and cooperative forces of natural selection have driven the evolution of intelligence for millions of years, culminating in nature's vast biodiversity and the complexity of human minds. Inspired by this process, we propose a novel multi-agent reinforcement learning framework where each agent is assigned a genotype and where reward functions are modelled after the concept of inclusive fitness. An agent's genetic material may be shared with other agents, and our inclusive reward function naturally accounts for this. We study the resulting social dynamics in two types of network games with prisoner's dilemmas and find that our results align with well-established principles from biology, such as Hamilton's rule. Furthermore, we outline how this framework can extend to more open-ended environments with spatial and temporal structure, finite resources, and evolving populations. We hypothesize the emergence of an arms race of strategies, where each new strategy is a gradual improvement over earlier adaptations of other agents, effectively producing a multi-agent autocurriculum analogous to biological evolution. In contrast to the binary team-based structures prevalent in earlier research, our gene-based reward structure introduces a spectrum of cooperation ranging from full adversity to full cooperativeness based on genetic similarity, enabling unique non team-based social dynamics. For example, one agent having a mutual cooperative relationship with two other agents, while the two other agents behave adversarially towards each other. We argue that incorporating inclusive fitness in agents provides a foundation for the emergence of more strategically advanced and socially intelligent agents.

Neural Information Processing Systems http://nips.cc/