Certain limitations in both the available expression **data** as well as NCA itself could be addressed to make this approach more powerful. Gene expression analyses obtained from whole blood leukocyte samples provide an integrated signal from different leukocyte populations which are difficult to deconvolute, and so using a single cell population would be advantageous, such as could be obtained using cell sorting or other methods. Additionally, the number of transcription factors which can be used in NCA is approximately the number of expression profiles in the **data** set, and so a greater number of expression profilesobtained at best shortly after the endotoxin administrationwould also have been useful. Finally, NCA's scaling property, which makes it difficult to predict the direction of transcription factor activity, as well as NCA's current inability to incorporate time course information from the **data** set are important limitations to the method. Some approaches that may overcome these challenges include recent studies in