As DNA sequencing technologies keep improving in scale and cost, there is a growing need to develop machine learning models to analyze DNA sequences, e.g., to decipher regulatory signals from DNA fragments bound by a particular protein of interest. As a double helix made of two complementary strands, a DNA fragment can be sequenced as two equivalent, so-called reverse complement (RC) sequences of nucleotides. To take into account this inherent symmetry of the data in machine learning models can facilitate learning. In this sense, several authors have recently proposed particular RC-equivariant convolutional neural networks (CNNs). However, it remains unknown whether other RC-equivariant architecture exist, which could potentially increase the set of basic models adapted to DNA sequences for practitioners. Here, we close this gap by characterizing the set of all linear RC-equivariant layers, and show in particular that new architectures exist beyond the ones already explored. We further discuss RC-equivariant pointwise nonlinearities adapted to different architectures, as well as RC-equivariant embeddings of $k$-mers as an alternative to one-hot encoding of nucleotides. We show experimentally that the new architectures can outperform existing ones.

The Ribonucleic Acid (RNA) inverse folding problem, designing nucleotide sequences that fold into specific tertiary structures, is a fundamental computational biology problem with important applications in synthetic biology and bioengineering. The design of complex three-dimensional RNA architectures remains computationally demanding and mostly unresolved, as most existing approaches focus on secondary structures. In order to address tertiary RNA inverse folding, we present BeeRNA, a bio-inspired method that employs the Artificial Bee Colony (ABC) optimization algorithm. Our approach combines base-pair distance filtering with RMSD-based structural assessment using RhoFold for structure prediction, resulting in a two-stage fitness evaluation strategy. To guarantee biologically plausible sequences with balanced GC content, the algorithm takes thermodynamic constraints and adaptive mutation rates into consideration. In this work, we focus primarily on short and medium-length RNAs ($<$ 100 nucleotides), a biologically significant regime that includes microRNAs (miRNAs), aptamers, and ribozymes, where BeeRNA achieves high structural fidelity with practical CPU runtimes. The lightweight, training-free implementation will be publicly released for reproducibility, offering a promising bio-inspired approach for RNA design in therapeutics and biotechnology.

RNA plays a pivotal role in translating genetic instructions into functional outcomes, underscoring its importance in biological processes and disease mechanisms.

This highlights an urgent need of contributions from the machine learning community.

In this section, we detail the datasets used during training and for our experiments.

This study investigates embedding reconstruction attacks in large language models (LLMs) applied to genomic sequences, with a specific focus on how fine-tuning affects vulnerability to these attacks. Building upon Pan et al.'s seminal work demonstrating that embeddings from pretrained language models can leak sensitive information, we conduct a comprehensive analysis using the HS3D genomic dataset to determine whether task-specific optimization strengthens or weakens privacy protections. Our research extends Pan et al.'s work in three significant dimensions. First, we apply their reconstruction attack pipeline to pretrained and fine-tuned model embeddings, addressing a critical gap in their methodology that did not specify embedding types. Second, we implement specialized tokenization mechanisms tailored specifically for DNA sequences, enhancing the model's ability to process genomic data, as these models are pretrained on natural language and not DNA. Third, we perform a detailed comparative analysis examining position-specific, nucleotide-type, and privacy changes between pretrained and fine-tuned embeddings. We assess embeddings vulnerabilities across different types and dimensions, providing deeper insights into how task adaptation shifts privacy risks throughout genomic sequences. Our findings show a clear distinction in reconstruction vulnerability between pretrained and fine-tuned embeddings. Notably, fine-tuning strengthens resistance to reconstruction attacks in multiple architectures -- XLNet (+19.8\%), GPT-2 (+9.8\%), and BERT (+7.8\%) -- pointing to task-specific optimization as a potential privacy enhancement mechanism. These results highlight the need for advanced protective mechanisms for language models processing sensitive genomic data, while highlighting fine-tuning as a potential privacy-enhancing technique worth further exploration.