Imagine a DNA sample containing a mixture of different intact plasmids. These samples are sequenced using either MiSeq or HiSeq sequencing. Would it possible to assemble these plasmids post-sequencing as they would have been when sequenced individually?
You would expect to have high coverage, given the plasmids are short, so de novo assembly would be likely very easy. Given that each plasmid is present in different multiples, you would expect different coverage on each plasmid, so it might be best to approach it as a metagenome-type or transcriptome assembly, rather than a classic genome assembly.
Alternatively, Google search just told me there is a tool called plasmidSPADES designed for just your purpose. SPADES itself is a reliable genome assembler, so I would imagine plasmidSPADES to be a good choice. It does assume that there is also some whole bacterial genomes in the sequencing mix though.
As @terdon commented, it does depend on whether you have many identical copies of each plasmid, or many similar but not identical plasmids in the mix.
Let's take a step back and consider the "perfect" output for a de novo assembly algorithm. Ideally, you would like to see one complete sequence for molecule (chromosome, plasmid, etc.). In reality, this is difficult to achieve due to a couple factors.
- By random chance some regions may have low coverage, meaning that there are an insufficient number of reads spanning the region to reconstruct it de novo.
- A bigger problem is that some portions of the genome are repetitive and occur at many different locations, sometimes even on different chromosomes.
So in practice, it's very common that de novo assemblies can only recover partial fragments of each molecule, and sometimes fragments are erroneously fused due to shared repetitive content.
Back to your question: it's certainly possible to assemble distinct plasmids that were sequenced together without any special sample prep. How well this will work in practice will depend on the amount of coverage/redundancy in the sequenced reads and the amount of DNA shared between the plasmids. If they don't share much in common, and you sample to a sufficient depth of coverage, you shouldn't have any problem assembling them.