At the moment, sequence assembly is still a big problem. A new genome is sequenced as a collection of short overlapping sequence pieces (short is usually anywhere between 32 and 500 bases at the moment), which then have to be painstakingly pieced together. There are errors in the sequencing, and repetitive regions, and this complicates the problem. The size of the data is also a problem. Plant genomes can have around 20 billion bases, so working with files and having enough memory to store data structures adds to the problem.
So much must have changed in de Bruijn's lifetime. Back in 1946 the structure of DNA was not clear. Watson and Crick's paper in 1953 was yet to come. Computers were yet to come. He wouldn't have known that more than 60 years later we'd be using his graphs to assemble whole genomes that were sequenced using the detection of fluoresence. What will we be doing 60 years from now that links maths, computer science, physics, chemistry and biology?