AI能否读懂人类基因组?Quanta长文提出质疑
这篇由 Quanta Magazine 发表、WIRED AI 转载的文章指出,人类基因组中仅约 2% 是编码蛋白质的基因序列,理解基因组的难点已不在于单个基因的功能,而在于基因如何被调控,而这可能涉及基因组其余的大部分。文章提到 Evo 2、Genos 和 Google DeepMind 的 AlphaGenome 等基因组“基础模型”,它们基于海量基因组数据训练,用于预测 DNA 序列差异如何影响生物过程乃至性状与疾病风险。作者认为这类“黑箱”计算虽可能有用,却无法带来对基因组运作的真正理解,因为染色质三维折叠、表观遗传标记等调控层意味着关键信息未必只存在于序列之中,基因组也可能并不符合输入—输出式的建模假设。
文章对基因组基础模型提出的质疑值得关注:若有研究者的论点成立,即相关调控信息本就存在于序列之外,那么这类模型预测突变后果的能力将存在边界。
The original version of this story appeared in Quanta Magazine.
Since its molecular structure was deduced in the 1950s, DNA has been hailed by many biologists as the secret of life. They’ve read and studied the information stored in the DNA found in the cells of living organisms, known as their genomes, and claimed that this genetic database must be some kind of blueprint, code script, or computer. But if DNA really does harbor some greater secret about how life works, biologists have yet to find it.
In fact, the human genome is less a script than a puzzle that gets harder the closer they look. Knowing the entire sequence—the order of all 3 billion or so of our DNA’s chemical building blocks, nearly fully deduced by the international Human Genome Project between 1990 and 2003—hasn’t helped much. That investigation showed that barely 2 percent of the human genome consists of actual genes, the information-coding sequences of DNA.
It’s now clear that understanding the human genome is no longer a matter of figuring out what each gene does. The deeper and much harder question is how those genes are used, or regulated, a question that seems to involve some and perhaps much of the rest of the genome. By switching suites of genes on and off, the many different cell types in our bodies can all be created from the same material. Cells also regulate their genes from moment to moment in response to a constant inflow of signals from their neighbors and surroundings. But the processes that govern gene regulation are proving so complex that some biologists wonder whether a full understanding of it—of how the genome really works—will ever be within the grasp of our puny minds.