Beyond Gene Reconstruction: Learning Cell Representations through Complementary Transcriptomic Views
The rapid growth of single-cell transcriptomic data has enabled the development of foundation models pretrained primarily by reconstructing masked expression values. This objective encourages these models to learn gene dependencies but does not directly optimize whole-cell representations, which are essential for many downstream tasks. To bridge this gap, we propose a contrastive pretraining framework that learns cell representations through complementary transcriptomic views. Since standard contrastive learning is not readily applicable to single-cell pretraining, we introduce specific adaptations along three dimensions --- co-expression-guided gene partitioning, expression-aware contrast-set construction, and competence-gated contrastive onset. Specifically, we first construct two complementary views of each cell by partitioning its genes according to their co-expression structure. Then, to prevent the model from using gene-set identity as a shortcut, we construct hard negatives by permuting expression values while keeping gene identities unchanged. Finally, we introduce a competence-aware controller to determine how the contrastive objective is applied. Experiments on cell-type annotation and gene regulatory network inference demonstrate competitive transfer under the evaluated protocols. In the six-network GRN evaluation, our method records the highest mean AUROC and AUPRC point estimates among the compared variants, while the highest-scoring variant differs across individual networks. These results establish complementary-view contrastive learning as an effective direction for single-cell pretraining beyond gene reconstruction.
Code (0)
등록된 구현이 없습니다.
Tasks
Contrastive LearningSimilar Papers 제목 키워드 기반
Viral Proteins Reveal Geometry of Protein Language Models
Protein language models are trained on highly imbalanced datasets, raising the question of how they represent underrepresented biological sequences. Using viral proteins as a case study across ESM model families, we iden…
Protein Language ModelPose-Free 3D Quantitative Phase Imaging of Flowing Cellular Populations
High-throughput 3D quantitative phase imaging (QPI) in flow cytometry enables label-free, volumetric characterization of individual cells by reconstructing their refractive index (RI) distributions from multiple viewing …
Physics-Informed Topological Signal Processing for Water Distribution Network Monitoring
Water management is one of the most critical aspects of our society, together with population increase and climate change. Water scarcity requires a better characterization and monitoring of Water Distribution Networks (…
One-bit Compressed Sensing using Generative Models
This paper addresses the classical problem of one-bit compressed sensing using a deep learning-based reconstruction algorithm that leverages a trained generative model to enhance the signal reconstruction performance. Th…
compressed sensingDomain Adaptive and Fine-grained Anomaly Detection for Single-cell Sequencing Data and Beyond
Fined-grained anomalous cell detection from affected tissues is critical for clinical diagnosis and pathological research. Single-cell sequencing data provide unprecedented opportunities for this task. However, current a…
Anomaly DetectionCell DetectionDomain Adaptation