Starting material is a huge problem. You need at least 50ng of DNA for an Illumina sequencing run, usually more if you want to sequence ultra deep, which you w

Starting material is a huge problem. You need at least 50ng of DNA for an Illumina sequencing run, usually more if you want to sequence ultra deep, which you will need for whole genome sequencing. For PCR you need at least 0.1ng (usually higher) of DNA. But a single cell has about 80 pg of DNA. So you need to amplify the DNA several orders of magnitude before you can apply standard PCR. Several approaches can solve this problem, DOP-PCR, MDA, MALBAC. But each results in biased amplification, with differing biases with each method. Source: I worked on the computational modeling of this problem in grad school, https://academic.oup.com/bioinformatics/article/30/22/3159/2391301 https://academic.oup.com/bioinformatics/article/30/22/3159/2...