Models for CST prediction will vary depending on what parameters need to be accounted for when constructing the model. Most parsimonious reconstruction (MPR)
Parsimony is the principle in which one chooses the simplest scientific explanation that fits the evidence. In terms of building phylogenetic trees, the best hypothesis is the one that requires the fewest evolutionary changes. Using parsimony to reconstruct ancestral character states on a phylogenetic tree is a method for testing ecological and evolutionary hypotheses. This method can be used in CST studies to estimate the number of character changes that exist between pathogens in relation to their host. This makes MPR useful for tracking a CST pathogen to its origins. MPR can also be used to the compare traits of host species populations. Traits and behaviours within a population could make them more susceptible to CST. For example, species which migrate regionally are important for spreading viruses through population networks.Despite the success of parsimony reconstructions, research suggests they are often sensitive and can sometimes be prone to bias in complex models. This can cause problems for CST models that have to consider many variables. Alternatives methods, such as maximum likelihood, have been developed as an alternative to parsimony reconstruction. Using genetic markers
Two methods of measuring genetic variation, variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs), have been very beneficial to the study of bacterial transmission.
A study on identification of viruses in bats that could spread to other mammals used the workflow:  sequencing of genomic samples → “cleaning” of raw reads → elimination of host reads and eukaryotic contaminants → de novo assembly of the remaining reads → annotation of viral contigs → molecular detection of specific viruses → phylogenetic analysis → interpretation of data.Detecting CST and estimating its rate based on prevalence data is challenging. Due to these difficulties, computational methods are used to analyse CST events and the pathogens associated with them. The explosive development of molecular techniques has opened new possibilities for using phylogenetic analysis of pathogen genetics to infer epidemiological parameters. This provides some insight into the origins of these events and how they could be addressed. Methods of CST prevention are currently using both biological and computational data. An example of this is using both cellular assays and phylogenetic comparisons to support a role for TRIM5α, the product of the TRIM5 gene, in suppressing interspecies transmission and emergence of retroviruses in nature. Analysis
Phylogeny
The comparison of genomic data is very important for the study of cross-species transmission. Phylogenetic analysis is used to compare genetic variation in both pathogens associated with CST and the host species that they infect. Taken together, it is possible to infer what allowed a pathogen to crossover to a new host (i.e. mutation in a pathogen, change in host susceptibility) and how this can be prevented in the future.