 This paper proposes a new approach to detect the predisease state of complex diseases using a single sample. The authors propose a novel index called Single Sample Culbac Libre Divergence, SKLD, to measure the disturbance caused by a case sample on the background. This index can be used to identify the critical state or tipping point of a biological system. The authors tested their method on several different types of cancer and found that it successfully identified the predisease state of these diseases. Furthermore, they also provided a set of SKLD signalling markers that could be used for further practical applications. This article was authored by J. U. N. Zhong, Rui Liu, and Pei Chen.