Abstract: A method of assembling a sequence representing pieces of at least one chromosome from a set of raw sub-sequences representing DNA fragments of a library including DNA fragments including chains of contiguous nucleotides and including DNA fragments including combinations of at least two chains of contiguous nucleotides. After having obtained first values representing contact frequencies between DNA regions, the first values being associated with second values representing distances between the corresponding DNA regions, the method includes: updating a genome structure based on the first and second values and based on a theoretical model associating a contact probability between DNA regions with a distance between the corresponding DNA regions, the updated genome structure being representative of the real genome structure of the chromosome; and updating parameters of the theoretical model as a function of the updated genome structure.