Although a homologous recombination event between human and swine viruses was proposed in this case, a later study showed that the phylogenetic incongruence in this case was entirely due to contrasting patterns of rate variation. Because of the important yet ongoing controversy over the occurrence of homologous RNA recombination in influenza A virus, we herein propose guidelines for how this process can be reliably detected. Scopoletin Laboratory artifacts for recombination are most likely to be present as single isolates in phylogenetic trees. However, the greater the frequency of this putative recombinant in the circulating virus population, the lesser the probability that it is a false-positive as this would require multiple identical errors to be made;Furagin this is particularly true if the putative recombinant is isolated by different laboratories. An important case in point concerns Ebola virus, where an entire recombinant lineage has been identified, and which also demonstrate that homologous RNA recombination can indeed occur sporadically in negativesense RNA viruses. Ideally, parental sequences should also appear as clades and not single sequences to ensure that putative parental sequences did not result from contamination or sequencing error. As described previously, Gibbs et al suggested that the HA segment of the 1918 H1N1 virus was a recombinant between a swine virus and a human virus. However, this claim was strongly refuted by Worobey et al, primarily because of a lack of phylogenetic support for the recombination signal and the inability to exclude the alternative hypothesis of lineage-specific rate variation. To provide some control for quality of sequencing, we can separate the database of all publicly available influenza sequences into those that were sequenced by the Influenza Genome Sequencing Project and those that were not. Importantly, sequence data generated under the IGSP are subject to very strict quality control, manifest as a high level of redundancy. Specifically, the sequencing procedure utilizes both short amplicons and overlapping amplicons, so that each nucleotide is covered by at least two separate amplicons and each amplicon is sequenced at least twice in both the forward and reverse directions.