The minimization of auto-ignition risk is critical to the design of premixers of high power aeroderivative gas turbines as an increased use of highly reactive future fuels (for example, hydrogen or higher hydrocarbons) is anticipated. Safety factors based on ignition delays of homogeneous mixtures are generally used to guide the choice of a residence time for a given premixer. However, auto-ignition chemistry under aeroderivative conditions is fast (0.5–2 ms) and can be initiated within typical premixer residence times. The analysis of what takes place in this short period necessarily involves the study of low-temperature auto-ignition precursor chemistry, but precursors can change with fuel and local reactivity. Chemical explosive modes (CEMs) are a natural alternative to study this as they can provide a measure for auto-ignition risk by considering the whole thermochemical state in the framework of an eigenvalue problem. When transport effects are included by coupling the evolution of the chemical explosive modes to turbulence, it is possible to obtain a measure of spatial auto-ignition risk where both chemical (e.g., ignition delay) and aerodynamic (e.g., local residence time) influences are unified. In this article, we describe a method that couples large eddy simulation (LES) to newly developed, reduced auto-ignition chemical kinetics to study auto-ignition precursors in an example premixer representative of real life geometric complexity. A blend of pure methane and di-methyl ether (DME), a common fuel used for experimental auto-ignition studies, was transported using the reduced mechanism (38 species/238 reactions) under engine conditions at increasing levels of DME concentrations until exothermic auto-ignition kernels were formed. The resolution of species profiles was ensured by using a thickened flame model where dynamic thickening was carried out with a flame sensor modified to work with multistage heat release. This paper is outlined as follows: First, a reduced mechanism is constructed and validated for modeling methane as well as DME auto-ignition. Second, sensitivity analysis is used to show the need for chemical explosive modes. Third, the thickened flame model modifications are described and then applied to an example premixer at 25 bar/890 K preheat. The chemical explosive mode analysis closely follows the large thermochemical changes in the premixer as a function of DME concentrations and identifies where the premixer is sensitive and flame anchoring is likely to occur.