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The ongoing explosion of genome sequence data is transforming how we reconstruct and understand the histories of biological systems. Across biological scales, from individual cells to populations and species, trees-based models provide a…

Populations and Evolution · Quantitative Biology 2025-12-08 Yun Deng , Shing H. Zhan , Yulin Zhang , Chao Zhang , Bingjie Chen

Gene expression prediction, which predicts mRNA expression levels from DNA sequences, presents significant challenges. Previous works often focus on extending input sequence length to locate distal enhancers, which may influence target…

Machine Learning · Computer Science 2026-03-13 Zhao Yang , Yi Duan , Jiwei Zhu , Ying Ba , Chuan Cao , Bing Su

Phylogenetic analyses of gene expression have great potential for addressing a wide range of questions. These analyses will, for example, identify genes that have evolutionary shifts in expression that are correlated with evolutionary…

Populations and Evolution · Quantitative Biology 2014-01-14 Casey W. Dunn , Xi Luo , Zhijin Wu

Generative modeling for protein engineering is key to solving fundamental problems in synthetic biology, medicine, and material science. We pose protein engineering as an unsupervised sequence generation problem in order to leverage the…

Understanding disease-gene associations is essential for unravelling disease mechanisms and advancing diagnostics and therapeutics. Traditional approaches based on manual curation and literature review are labour-intensive and not scalable,…

Machine Learning · Computer Science 2026-02-24 Osman Onur Kuzucu , Tunca Doğan

Each human genome is a 3 billion base pair set of encoding instructions. Decoding the genome using deep learning fundamentally differs from most tasks, as we do not know the full structure of the data and therefore cannot design…

Machine Learning · Computer Science 2016-05-24 Laura Deming , Sasha Targ , Nate Sauder , Diogo Almeida , Chun Jimmie Ye

Understanding the mechanisms of interactions within cells, tissues, and organisms is crucial to driving developments across biology and medicine. Mathematical modeling is an essential tool for simulating biological systems and revealing…

Molecular Networks · Quantitative Biology 2024-08-13 Lingxia Qiao , Ali Khalilimeybodi , Nathaniel J Linden-Santangeli , Padmini Rangamani

Next-generation sequencing technologies have enhanced the scope of Internet-of-Things (IoT) to include genomics for personalized medicine through the increased availability of an abundance of genome data collected from heterogeneous sources…

DNA language models have advanced genomics, but their downstream performance varies widely due to differences in tokenization, pretraining data, and architecture. We argue that a major bottleneck lies in tokenizing sparse and unevenly…

Genomics · Quantitative Biology 2025-12-23 Xiaoxiao Zhou , Zihan Wang , Jingbo Shang , Yang E. Li

Developing models with high interpretability and even deriving formulas to quantify relationships between biological data is an emerging need. We propose here a framework for ab initio derivation of sequence motifs and linear formula using…

Quantitative Methods · Quantitative Biology 2022-08-23 Chengyu Liu , Wei Wang

Understanding how genetic variants influence cellular-level processes is an important step towards understanding how they influence important organismal-level traits, or "phenotypes", including human disease susceptibility. To this end…

Methodology · Statistics 2013-07-30 Heejung Shim , Matthew Stephens

Language models based on the Transformer architecture achieve excellent results in many language-related tasks, such as text classification or sentiment analysis. However, despite the architecture of these models being well-defined, little…

Computation and Language · Computer Science 2025-04-14 Miguel López-Otal , Jorge Gracia , Jordi Bernad , Carlos Bobed , Lucía Pitarch-Ballesteros , Emma Anglés-Herrero

There is considerable interest in predicting the pathogenicity of protein variants in human genes. Due to the sparsity of high quality labels, recent approaches turn to \textit{unsupervised} learning, using Multiple Sequence Alignments…

Machine Learning · Computer Science 2022-12-09 Allan Zhou , Nicholas C. Landolfi , Daniel C. O'Neill

This paper presents the Ensemble Nucleotide Byte-level Encoder-Decoder (ENBED) foundation model, analyzing DNA sequences at byte-level precision with an encoder-decoder Transformer architecture. ENBED uses a sub-quadratic implementation of…

Machine Learning · Computer Science 2024-08-26 Aditya Malusare , Harish Kothandaraman , Dipesh Tamboli , Nadia A. Lanman , Vaneet Aggarwal

DNA language models are increasingly used to represent genomic sequence, yet their effectiveness depends critically on how raw nucleotides are converted into model inputs. Unlike natural language, DNA offers no canonical boundaries, making…

Genomics · Quantitative Biology 2026-05-21 Taewon Kim , Jihwan Shin , Hyomin Kim , Youngmok Jung , Jonghoon Lee , Won-Chul Lee , Sungsoo Ahn , Insu Han

We introduce Gene42, a novel family of Genomic Foundation Models (GFMs) designed to manage context lengths of up to 192,000 base pairs (bp) at a single-nucleotide resolution. Gene42 models utilize a decoder-only (LLaMA-style) architecture…

Cancer is a term that denotes a group of diseases caused by abnormal growth of cells that can spread in different parts of the body. According to the World Health Organization (WHO), cancer is the second major cause of death after…

Machine Learning · Computer Science 2023-01-31 Fadi Alharbi , Aleksandar Vakanski

Motivation: The rapid growth of diverse biological data allows us to consider interactions between a variety of objects, such as genes, chemicals, molecular signatures, diseases, pathways and environmental exposures. Often, any pair of…

Machine Learning · Computer Science 2017-08-14 Marinka Zitnik , Blaz Zupan

The Genomic Foundation Model (GFM) paradigm is expected to facilitate the extraction of generalizable representations from massive genomic data, thereby enabling their application across a spectrum of downstream applications. Despite…

Genomics · Quantitative Biology 2024-06-06 Zicheng Liu , Jiahui Li , Siyuan Li , Zelin Zang , Cheng Tan , Yufei Huang , Yajing Bai , Stan Z. Li

The association of a given human phenotype to a genetic variant remains a critical challenge for biology. We present a novel system called PhenoLinker capable of associating a score to a phenotype-gene relationship by using heterogeneous…

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