Modeling cannabinoids from a large-scale sample ofCannabis sativachemotypes

Abstract

33The accelerating legalization of Cannabis has opened the industry to using contemporary 34 analytical techniques. The gene regulation and pharmacokinetics of dozens of cannabinoids 35 remain poorly understood. Because retailers in many medical and recreational 36 jurisdictions are required to report chemical concentrations of cannabinoids, commercial 37 laboratories have growing chemotype datasets of diverse Cannabis cultivars. Using a data 38 set of 17,600 cultivars tested by Steep Hill Inc., we apply machine learning techniques to 39 interpolate missing chemotype observations and cluster cultivars together based on 40 similarity. Our results show that cultivars cluster based on their chemotype, and that some 41 imputation methods work better than others at grouping these cultivars based on 42 chemotypic identity. However, due to the missing data for some of the cannabinoids their 43 behavior could not be accurately predicted. These findings have implications for 44 characterizing complex interactions in cannabinoid biosynthesis and improving 45 phenotypical classification of Cannabis cultivars.

Genomic description of critical upstream cannabinoid biosynthesis genes

“…If this is the case, and other oxidocyclase genes are producing the THCA and or CBDA compounds, it will make it hard for farmers to produce compliant hemp below the 0.3% THC regulated limit. This result supports the idea that the enzymes codified by these oxidocyclase genes are both promiscuous (Onofri et al 2015; Vergara et al 2020) and sloppy (Auldridge et al 2006; Franco 2011; Chakraborty et al 2013; Zirpel et al 2018; Vergara et al 2020).…”

“…However, despite low productions of CBCA, expression levels of this gene varies between C. sativa varieties (Allen et al 2022). As previously suggested, perhaps CBCAS is the sloppiest of all synthases in the pathway (Vergara et al 2020). Similarly, the genes whose products remain to be established are interesting due to their large number.…”

“…The diversity, evolutionary origin, function, and genomic context of the Cannabinoid oxidocyclase genes, the last step of the pathway, have been characterized previously (Laverty et al 2019; van Velzen and Schranz 2020; Grassa et al 2021). These genes are highly similar at the structural and genetic sequence levels and the enzymes they code for may be classified as “promiscuous” as they act on the same substrate (Onofri et al 2015; Vergara et al 2019; Vergara et al 2020). In their function as synthases, they may also exhibit “sloppiness” (Auldridge et al 2006; Franco 2011; Chakraborty et al 2013; Vergara et al 2020): in vitro , they can produce up to eight different products, including each other’s compounds (Zirpel et al 2018).…”

“…These genes are highly similar at the structural and genetic sequence levels and the enzymes they code for may be classified as “promiscuous” as they act on the same substrate (Onofri et al 2015; Vergara et al 2019; Vergara et al 2020). In their function as synthases, they may also exhibit “sloppiness” (Auldridge et al 2006; Franco 2011; Chakraborty et al 2013; Vergara et al 2020): in vitro , they can produce up to eight different products, including each other’s compounds (Zirpel et al 2018). The genes encoding these synthases are likely derived from the same ancestral gene via duplication events (Onofri et al 2015; Padgitt-Cobb et al 2019; van Velzen and Schranz 2020) and are located in close proximity in the genome (Laverty et al 2019; van Velzen and Schranz 2020; Grassa et al 2021).…”

Genomic Evidence That Governmentally Produced Cannabis sativa Poorly Represents Genetic Variation Available in State Markets

“…However, oversight is needed to assure the quality and consistency of Cannabis testing across laboratories (Jikomes and Zoorob, 2018). Regulation and supervision will allow for a deeper understanding of all the compounds produced by the plant, particularly minor cannabinoids which are not always measured (Vergara et al, 2020) and are produced using multiple genes with complex interactions (Vergara et al, 2019). This is particularly important because medical Cannabis use has outpaced its research (Hutchison et al, 2019).…”