How to start with a new Sanskrit manuscript?

Suppose you have in front of you a manuscript in a foreign script (although you know the language) and you do not have a copy of the text in a known script. How do you start your journey in the manuscript?

After three tough days, I could finally decrypt some words in a manuscript written in some form of grantha I was not acquainted with (possibly halfway between grantha-tamil and grantha-malayalam). It costed me time and energy and I wonder whether someone ever wrote an easy-to-follow guide to lead one's first steps within a manuscript. Do you know of any such guide? And what do you do first in similar situations? I will start sharing my (limited) experience.

1. 1. Bibliographical resources: I am very grateful to R. Grünendahl for his South Indian Scripts in Sanskrit Manuscripts and Prints (Grantha Tamil, Malayalam, Telegu, Kannada, Nandinagari), with great tables. Unfortunately, the fonts used (the book was published in 2001) are the ones now common in print and are usually far away from the characters one finds in manuscripts. More important, there is no indication about the ductus of a graphe, i.e., one does not learn where does a scribe start while writing, e.g., a ka. Consequently, one is not in the position to foresee possible variations in the final result.
2. 2. Human resources: This is possibly the most important element. When I first started reading mālāyālam, a friend, Pratibhā Chelaparampath, taught me the script the way she learnt it as a child. Manuscripts are quite different, but still this helped me a lot in getting an idea of the ductus of each letter. Besides, more expert colleagues have often made my work on manuscript much easier and enjoyable by sharing their charts of characters with me or even just by looking at the manuscript with me (I am particularly grateful to Alessandro Graheli for a great insight on the manuscript I am currently working on).
3. 3. Inference: Marks which are constantly repeated in a South Indian manuscript are likely to be vowel-marks. Once you have individuated some plausible candidates, you can check whether they come before or after any given "consonant". If the former, they might indicate an 'e' or an 'o'. A further evidence is acquired if one encounters them twice before a consonants (thus indicating an 'ai'). A "ca" ('and') should also be very common. Pauses, such as the ones marked by daṇḍas are useful to start a new inquiry in case the preceding one has yield no result…
4. 4. Psychology: Don't despaire. I try to remember that there is always a moment when I am tempted to give up, but that I always overcome it.