Say I have sequenced the whole-genome of an individual or set of individuals. I have some task at hand, and need to decide whether I want to just align the reads to e.g. GRCh38, or if I want to de novo assemble each whole-genome. I imagine there are pros and cons with both methods, and as such which method I should choose depends on the task at hand. Is this the case? What are the differences?
De novo assembly would be used primarily when we expect to see large-scale variations that are not present in the reference genome.
Or alternatively when the variations are such that aligning the reads to the reference genome would produce confusing or ambiguous alignments from which we would be unable to correctly reconstruct the original sequence.