Cherry Kevin M, Qian Lulu
Bioengineering, California Institute of Technology, Pasadena, CA, USA.
Computer Science, California Institute of Technology, Pasadena, CA, USA.
Nature. 2025 Sep 3. doi: 10.1038/s41586-025-09479-w.
Learning enables biological organisms to begin life simple yet develop immensely diverse and complex behaviours. Understanding learning principles in engineered molecular systems could enable us to endow non-living physical systems with similar capabilities. Inspired by how the brain processes information, the principles of neural computation have been developed over the past 80 years, forming the foundation of modern machine learning. More than four decades ago, connections between neural computation and physical systems were established. More recently, synthetic molecular systems, including nucleic acid and protein circuits, have been investigated for their abilities to implement neural computation. However, in these systems, learning of molecular parameters such as concentrations and reaction rates was performed in silico to generate desired input-output functions. Here we show that DNA molecules can be programmed to autonomously carry out supervised learning in vitro, with the system learning to perform pattern classification from molecular examples of inputs and desired responses. We demonstrate a DNA neural network trained to classify three different sets of 100-bit patterns, integrating training data directly into memories of molecular concentrations and using these memories to process subsequent test data. Our work suggests that molecular circuits can learn tasks more complex than simple adaptive behaviours. This opens the door to molecular machines capable of embedded learning and decision-making in a wide range of physical systems, from biomedicine to soft materials.
学习使生物有机体能够以简单的方式开启生命历程,但随后发展出极其多样和复杂的行为。理解工程分子系统中的学习原理能够使我们赋予无生命的物理系统类似的能力。受大脑处理信息方式的启发,神经计算原理在过去80年里得以发展,构成了现代机器学习的基础。四十多年前,神经计算与物理系统之间建立了联系。最近,包括核酸和蛋白质电路在内的合成分子系统因其实现神经计算的能力而受到研究。然而,在这些系统中,诸如浓度和反应速率等分子参数的学习是在计算机上进行的,以生成所需的输入-输出函数。在此,我们展示了DNA分子可以被编程在体外自主进行监督学习,该系统从输入和期望响应的分子示例中学习执行模式分类。我们展示了一个经过训练以对三组不同的100位模式进行分类的DNA神经网络,它将训练数据直接整合到分子浓度记忆中,并利用这些记忆来处理后续的测试数据。我们的工作表明分子电路能够学习比简单适应性行为更复杂的任务。这为能够在从生物医学到软材料等广泛物理系统中进行嵌入式学习和决策的分子机器打开了大门。