Search arXiv⌕ Search

arXiv · 2610.03815

GCTAg: scalable mixed-model analysis for biobank-scale agricultural cohorts

Abstract

Genome-wide association studies identify genomic variants associated with traits. Mixed linear model association (MLMA) methods using a whole-genome relationship matrix, such as those implemented in GCTA, are powerful but computationally expensive. Here, we remove key memory and CPU bottlenecks in GCTA, reducing REML memory usage by nearly 75% and substantially accelerating MLMA by orders of magnitude in biobank-scale cohorts while preserving exactness. We further exploit relatedness in the mapping cohort through a reduced-rank Woodbury matrix approach, delivering further orders of magnitude performance gains with controlled genomic inflation. Native on-the-fly dominance recoding also eliminates slow I/O-operations on intermediate files, enabling efficient additive and dominance MLMA analyses in large agricultural cohorts.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Alexander S. Leonard, Qiongyu He, Natasha Watson, Naveen Kumar Kadri, Hubert Pausch. 2026-10-01. GCTAg: scalable mixed-model analysis for biobank-scale agricultural cohorts. https://arxiv.org/abs/2610.03815

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Generating eukaryotic reference genome assemblies: Earth BioGenome Project quality standards and recommendations

Reference genome assemblies are foundational resources across the biological sciences as they begin to expose the fundamental building blocks of each species and the molecular toolkits vital for adaptation and survival. High-quality genomes enable insights into evolution, facilitate ecosystem monitoring and protection and conservation of species, access to new biomaterials and biomedicine, advances in agri- and aquaculture, and support planetary health. The amount of information gathered from a species' genome assembly is directly dependent on its quality. However, different sequencing technologies and software solutions generate a wide range of quality outcomes. Here, the Earth BioGenome Project's Sequencing and Assembly committee, together with a large community of researchers performing eukaryote sequencing and assembly, outlines quality standards for a "reference" assembly and formulates recommendations to ensure these standards are met.

q-bio.GN↗

WTKO-CNN: Deep Learning Reveals Sequence Motifs Distinguishing Wild-Type and Knockout ATAC-seq Peaks

Chromatin regulators can alter transcriptional programs by modifying the accessibility of regulatory DNA elements. Understanding how regulatory sequences differ between wild-type (WT) and knockout (KO) conditions is crucial for deciphering transcriptional control. Here, we applied a convolutional neural network, \textbf{WTKO-CNN} with an attention mechanism to classify DNA sequences as WT or KO, achieving high predictive performance. To interpret the model, we generated saliency maps to identify nucleotide positions most influential for the classification decision. From these high-saliency regions, we extracted and clustered k-mers, enabling de novo motif discovery. Sequence logos and consensus motifs derived from the CNN filters revealed biologically meaningful patterns, which are further validated using MEME, TOMTOM, and HOMER against known transcription factor binding sites. Our analysis identified motifs associated with transcription factor families that discriminate WT from KO sequences, demonstrating that CNN-guided saliency mapping is a powerful approach for uncovering functional sequence features.

q-bio.GN↗

CellMSA: Context Modeling for Single-Cell Representation Learning

Single-cell transcriptomics enables profiling of cellular states at unprecedented resolution, but its high dimensionality, sparsity, and technical batch effects pose significant challenges for representation learning. Existing single-cell foundation models typically encode each cell independently or only model cells from the same batch for denoising, thereby underutilizing the rich relational information across batches and cell types to model gene expression patterns. We argue that single-cell models can benefit from more informative cell-context modeling. By comparing consistency and variation across cells, models can capture fine-grained gene-gene dependencies associated with cell states, which are essential for learning high-quality representations. Inspired by the use of multiple sequence alignment (MSA) context in protein modeling, we propose CellMSA, a single-cell representation learning framework that introduces an MSA-inspired inductive bias into transcriptomic modeling. For each target cell, CellMSA retrieves relevant cells from different batches and biologically related cell types as context, and summarizes cross-cell patterns into a context-dependent gene-pair representation. This representation is then injected into a pair-aware target-cell encoder for fine-grained representation learning. We pretrain CellMSA on a large-scale human single-cell corpus of approximately 109 million cell observations, including 65.6 million primary observations. Experiments show that our framework consistently outperforms existing methods across multiple benchmarks. Code is available at the following repository: https://github.com/PharMolix/CellMSA.

q-bio.GN↗