改进图像压缩模型以更好保留染色质接触图的关键生物结构
HiFiC-G: Adapting HiFiC for Hi-C Contact Matrices

- 用空间加权损失和绝缘性惩罚项增强压缩模型的生物学敏感度
- 在两种细胞系中显著提升环状结构与拓扑关联域边界的保留率
- 适合基因组学研究者关注压缩对下游分析的影响
我们研究了高保真生成图像压缩(HiFiC)的损失设计是否可适配于保持染色质接触图(Hi-C)在有损压缩下的生物意义结构。标准图像压缩优化人类视觉感知,但Hi-C接触图以数值矩阵形式存储(.cool/.mcool),供下游基因组分析工具直接使用。过度压缩虽对人眼可视效果尚可,却可能模糊或删除分析依赖的环结构与拓扑关联域(TAD)边界。我们修改了HiFiC的失真项,引入空间加权均方误差,强化对环、TAD边界、条带及区室结构等生物显著区域的权重,并增加绝缘得分损失项以惩罚TAD边界模糊。采用三阶段微调策略,在不造成灾难性遗忘的前提下将预训练的HiFiC模型适配至Hi-C领域。评估显示,新系统HiFiC-G在两种细胞系上,不仅提升了传统图像质量指标(PSNR、SSIM),更在环/拓扑关联域/区室/条带保留率上表现优异。尽管局部结构(条带、TAD边界)保留远超指标预期,长程区室结构仍保留较差,该差距与基因组尺度相关,且源于固定尺寸分块架构——这正是原版HiFiC及其变体为内存效率所采用的设计限制。
原文摘要 · Abstract (English)
We study whether the loss design of High-Fidelity Generative Image Compression (HiFiC), a GAN-based neural codec originally built for natural photographs, can be adapted to preserve biologically meaningful structure in Hi-C chromatin contact maps under lossy compression. Standard image compression, including HiFiC in its original form, optimizes for human visual perception; but a Hi-C contact map is normally distributed together with its numeric matrix file (.cool/.mcool), which downstream genomic analysis tools consume directly. Aggressive compression that looks acceptable to the eye can nonetheless blur or delete loops and topologically associating domain (TAD) boundaries that these tools depend on. We modify HiFiC's distortion term with a spatially-weighted MSE that up-weights biologically salient regions (loops, TAD boundaries, stripes, compartment structure) and add an insulation-score loss term that directly penalizes loss of TAD boundary sharpness. We describe a three-phase fine-tuning strategy that adapts a pretrained HiFiC checkpoint to the Hi-C domain without catastrophic forgetting. We evaluate the resulting system, HiFiC-G, using both conventional image-quality metrics (PSNR, SSIM) and genomics-domain preservation metrics (loop/TAD/compartment/stripe preservation percentage) across two cell lines. HiFiC-G preserves local structure, meaning stripes and TAD boundaries, substantially better than the metrics alone would suggest, while long-range A/B compartment structure remains poorly preserved; we show this gap tracks genomic scale and is consistent with a specific architectural cause, the fixed-size tiling that both HiFiC-G and the original HiFiC rely on for memory efficiency.
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