bistro: An R package for vector bloodmeal identification by short tandem repeat overlap

Abstract

1. Measuring vector-human contact in a natural setting can inform precise targeting of interventions to interrupt transmission of vector-borne diseases. One approach is to directly match human DNA in vector bloodmeals to the individuals who were bitten using genotype panels of discriminative short tandem repeats (STRs). Existing methods for matching STR profiles in bloodmeals to the people bitten preclude the ability to match most incomplete profiles and multi-source bloodmeals to bitten individuals. 2. We developed bistro, an R package that implements 3 preexisting STR matching methods as well as the package's namesake, bistro, a new algorithm described here. bistro employs forensic analysis methods to calculate likelihood ratios and match human STR profiles in bloodmeals to people using a dynamic threshold. We evaluated the algorithm's accuracy and compared it to existing matching approaches using a publicly-available panel of 188 single-source and 100 multi-source samples containing DNA from 50 known human sources. Then we applied it to match 777 newly field-collected mosquito bloodmeals to a database of 645 people. 3. The R package implements four STR matching algorithms in user-friendly functions with clear documentation. bistro correctly matched 99% (184/185) of profiles in single-source samples, and 63% (225/359) of profiles from multi-source samples, resulting in a sensitivity of 0.75 (vs < 0.51 for other algorithms). The specificity of bistro was 0.9998 (vs. 1 for other algorithms). Furthermore, bistro identified 80% (729/909) of all possible matches for field-derived mosquitoes, yielding 1.4x more matches than existing algorithms. 4. bistro identifies more correct bloodmeal-human matches than existing approaches, enabling more accurate and robust analyses of vector-human contact in natural settings. The bistro R package and corresponding documentation allow for straightforward uptake of this algorithm by others.

Mosquito and human characteristics influence natural Anopheline biting behavior andPlasmodium falciparumtransmission

“…However, despite these limitations we were still able to estimate the maximum human-to-mosquito transmission efficiency to be between 0.14-0.27, which aligns with what has been observed in direct- and membrane-feeding experiments (11, 67, 68). Second, we could not match all mosquito STR profiles to people; however, our ability to incorporate a portion of incomplete and multisource profiles into our analysis increased our sample size by 37% (28), allowing us to more accurately use the matched bloodmeals and human infection data to estimate potential contributions to the transmission reservoir of different groups of people.…”

“…Mosquito bloodmeals were matched to cohort participants using the bistro R package (v0.2.0; (28)), which can provide matches for incomplete STR profiles and bloodmeals derived from multiple human sources. Briefly, matches based on weight-of-evidence likelihood ratios were determined for each mosquito-human pair and individual mosquito-based thresholds.…”

“…We genotyped human blood in both a DBS from each participant and in each mosquito abdomen classified as bloodfed for which a blood spot was available (1064/1563). We extracted gDNA from each sample type using Chelex-100, and genotyped using the Promega Geneprint 10 assay as described in Lapp et al (28).…”

Plasmodium falciparum infection in humans and mosquitoes influence natural Anopheline biting behavior and transmission

“…However, mosquitoes that evaded capture are likely a random sample of the overall population and are not expected to be biased toward one specific group of participants. Finally, we could not match all mosquito STR profiles to people indicating some bites may have been on individuals not enrolled in our study; however, our ability to incorporate a portion of incomplete and multisource profiles into our analysis increased our sample size by 37% 46 , allowing us to more accurately use the matched bloodmeals and human infection data to estimate potential contributions to the transmission reservoir of different groups of people. Additionally, these estimates assume equal transmission efficiency and gametocyte carriage amongst groups, which several studies have shown are also heterogeneous and nonrandom.…”

“…We genotyped human blood in both a DBS from each participant and in each mosquito abdomen classified as bloodfed for which a blood spot was available (1064/1563). We extracted gDNA from each sample type using Chelex-100, and genotyped using the Promega Geneprint 10 assay as described in Lapp et al 46 . This assay does not amplify non-human blood sources.…”