As compared with automatic profiling, which produces a noise profile in one step, manual profiling is done in two sub-steps with two noise analyzers used (you have to use the Advanced mode to use these analyzers; see the Tools | Advanced Mode menu item). The Rough Analyzer is used to do the initial analysis of the image noise; it produces a rough noise profile. The Fine-Tuning Analyzer improves the initial analysis and produces a fine-tuned noise profile.
Both Rough Analyzer and Fine-Tuning Analyzer use uniform image areas to measure the noise properties. If the image has uniform areas that contain noise without visible important image details, Neat Image can analyze the noise properties using these areas. During manual profiling, Neat Image does not automatically find these uniform areas (or areas that contain no details important to you), so you have to manually specify areas that it should analyze. A uniform area (with minor variation in all color channels) may be overcast sky, clear sky (without clouds and birds), or any other part of an image with no visually perceptible details (except the noise).