I know that the discrete raw counts from the RNA-Seq data are usually modeled by a negative binomial or a Poisson distribution, but what I am working on are the FPKM (Fragments Per Kilobase of transcript per Million mapped reads) values which represent a transformation of the raw values. They are continuous except many actual 0s. What is the probability distribution FPKM values are likely to follow, or are assumed to follow? Even after taking logarithm twice (after replacing 0s with 1, of course), the data does not follow a normal distribution since there are a lot of 0s.
FPKM/TPM values are generally log-normally distributed. Reference : Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels
Cuffdiff is one the tools that deals FPKM data for analysis of differential expression.By default they use the negative binomial with some condition specific parameter to avoid biases. There are some other models also available in Cuffdiff. Check the following documents for more details,