可解释的机器学习揭示了在产前症风险预测中的核糖体生物生成生物标志物
Jingjing Chen1, Dan Zhang1, Chengxiu Zhu1
1Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Wenzhou Medical University, Rui'an, China.
Frontiers in immunology
|June 24, 2025
概括
这项研究揭示了核糖体生物发生失调是孕前症 (PE) 的关键因素. 机器学习为早期PE检测和潜在的治疗目标确定了六种新生物标志物.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 生殖医学 生殖医学
背景情况:
- 孕前 (PE) 是一种主要的妊娠并发症,在全球范围内影响2-8%的怀孕.
- 目前的诊断方法依赖于晚期的临床症状,缺乏敏感的生物标志物.
- 需要早期的分子预测因子来改善孕产妇和胎儿的健康状况.
研究的目的:
- 通过使用胎盘转录基因数据,研究妊娠前的核糖体生物发生失调.
- 确定用于早期PE检测的新型分子生物标志物.
- 探索核糖体生物发生和PE病变发生之间的机制联系.
主要方法:
- 整合了两个胎盘转录基因数据集 (GSE75010,GSE10588).
- 进行了功能丰富和加权基因共同表达网络分析.
- 使用机器学习 (随机森林,SHAP) 来识别生物标志物和模型可解释性.
- 在临床样本上使用qRT-PCR验证的验证结果.
主要成果:
- 确定了25个与核糖体生物发生相关的差异表达基因.
- 优先考虑七个枢纽基因,其中六个被选择用于预测模型 (GLUL,DDX28,NCL,RIOK1,SUV39H1,RRS1).
- 实现了高诊断性能 (AUC 0.972培训,0.917验证),SUV39H1被确定为关键风险贡献者.
- 在临床PE样本中确认GLUL,NCL,DDX28和RIOK1的差异表达.
结论:
- 核糖体生物发生是一个关键的分子机制在先兆子的发病.
- 六个已识别的基因作为早期PE诊断的有希望的生物标志物.
- 需要进一步的研究来将这些发现转化为诊断和治疗的临床应用.
相关概念视频
Ribosome Profiling
3.6K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.6K
The Nucleolus
9.2K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
9.2K
Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
Regression Toward the Mean
6.5K
Regression toward the mean (“RTM”) is a phenomenon in which extremely high or low values—for example, and individual’s blood pressure at a particular moment—appear closer to a group’s average upon remeasuring. Although this statistical peculiarity is the result of random error and chance, it has been problematic across various medical, scientific, financial and psychological applications. In particular, RTM, if not taken into account, can interfere when...
6.5K
Improving Translational Accuracy
11.9K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.9K
Translation
15.7K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
15.7K


