不依赖补全,直接用残缺基因数据预测生存期。
SHIFT: Survival Prediction from Incomplete and Heterogeneous Genomic Data

- 用自注意力机制处理缺失基因数据,只基于实际观测值计算
- 在多种癌症数据集上表现优于传统模型和补全方法
- 可直接用部分数据的患者训练,提升跨中心预测能力
基因组预测模型常因不同机构使用不同测序面板而难以迁移,导致部署时出现结构化特征缺失。现有方法多限制于共有的基因、排除不完整患者或依赖测试时补全,均影响模型鲁棒性并限制多中心数据利用。本文提出SHIFT:一种缺失感知的生存预测模型,无需测试时补全即可直接从不完整基因组输入中预测。它对每个基因特征单独建模,结合掩码自注意力与特征可用性掩码,使预测仅基于已观测数据;训练中引入变率特征掩码以增强对异质缺失模式的鲁棒性。在胶质母细胞瘤和肺鳞状细胞癌数据上进行外部验证,涵盖严重跨队列面板差异的挑战场景。SHIFT在各类设置下均表现出强泛化能力,优于标准生存基线和基于补全的方法,且单一模型适配不同特征集。还发现,在开发中纳入不完整队列患者能提升外部数据表现,表明部分观测队列无需被排除。结果支持缺失感知建模是精准肿瘤学中多中心生存预测的实用策略。
原文摘要 · Abstract (English)
Genomic prediction models often fail to transfer across institutions because sequencing panels differ across sites, creating structural feature missingness at deployment. Existing approaches to this challenge typically restrict analysis to genes shared across cohorts, exclude patients with incomplete profiles, or rely on test-time imputation, all of which can reduce robustness and limit the use of multi-center data. We propose Survival prediction Handling Incomplete Features using Transformer (SHIFT), a missingness-aware survival model that directly predicts from incomplete genomic inputs without test-time imputation. SHIFT represents each genomic feature separately and uses masked self-attention, along with a feature-availability mask, so that predictions are based only on observed inputs. Further, we introduce variable-rate feature masking during training to improve robustness to heterogeneous missingness patterns. We evaluate the approach on glioblastoma and lung squamous cell carcinoma with external validation across multiple cohorts, including a challenging setting with severe cross-cohort panel mismatch. Across these settings, SHIFT shows strong generalization and compares favorably with standard survival baselines and imputation-based approaches, while using a single model across differing feature sets. We also find that incorporating patients from incomplete cohorts during development can improve performance on external data, suggesting that partially observed cohorts need not be excluded from model building. These results support missingness-aware modeling as a practical strategy for multi-center survival prediction in precision oncology.
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