So brilliant that #GEM2021 registration was made free this year! Awesome talks during Session 1 already! Wendy O'Meara discussed identification of #malaria reservoirs in Kenya! Check out the work in nature.com/articles/s4146… #Plasmodium
Xue Li also gave an excellent talk on spatial analysis of parasite population genomics during #malaria elimination efforts on Myanmar, citing samples collected during this incredible study: thelancet.com/journals/lance… #GEM2021 #Plasmodium
One more of the Session 1 #GEM2021 talks was by Eline Kattenberg (@ElineKattenberg), detailing the multiplexed Ampliseq targetted NGS assays that can be used for molecular surveillance of Pf or Pv isolates! The P. vivax preprint can be found at biorxiv.org/content/10.110… #malaria
A few notes from #GEM2021 Session 2 on Insecticide Resistance: Charles Wondji of @LSTMvector gave a fantastic talk, describing vector control, pyrethroids, & molecular mechanisms of resistance such as in stm.sciencemag.org/content/11/484… AND onlinelibrary.wiley.com/doi/full/10.11… #malaria
The second Insecticide Resistance talk was from Damaris Matoke-Muhia (@kwambo_2) (always a fantastic presenter!) who explained so much about Sustainable Development Goals (to end #malaria epidemics by 2030), & that molecular surveillance of vectors will need to be a part of that!
A 3rd talk by Chris Clarkson (@c_s_clarkson) at #GEM2021 added nicely to @kwambo_2's introduction to large-scale vector genomics! Dr Clarkson updated us on the Ag1000G Phase 3 data (available at malariagen.net/ag3) incl. possible SNPs for organophosphate resistance! #malaria
Dr Clarkson cited this paper which has some lovely maps of the insecticides used for IRS, including organophosphates: malariajournal.biomedcentral.com/articles/10.11… Of note, Dr Clarkson said that early Anopheles samples were collected before organophosphate usage, so future resistance will be monitored
The final, non-lightning talk of the #GEM2021 Insecticide Resistance session was from Penelope Hancock at Imperial College! Dr Hancock focussed on the frequencies of two Vgsc mutations across 9 African countries from 2005-2017! Check out some of the work: malariajournal.biomedcentral.com/articles/10.11…
And a quick note about the 4 fantastic #GEM2021 lightning talks for the Insecticide Resistance session: big mentions of metabolic enzyme mutations that confer insecticide resistance incl. CYP325A, CYP4c3, CYP9f2, CYP6aa1.. here's one mentioned preprint: biorxiv.org/content/10.110…
Day 2 of #GEM2021 was another whopper! Dr Nguyen Thanh Thuy Nhien started off the "Drug Resistance" session with some highlights from this huge dataset: medrxiv.org/content/10.110… ART resistance is a big concern in Vietnam & neighbouring regions. Sensitivity to mefloquine still tho!
In the 2nd #GEM2021 Drug Resistance talk, Dr Yaye Die Ddiaye of Chiekh Anta Diop University outlined some of her findings during molecular monitoring of #Plasmodium falciparum in Sénégal from 2015-2019 to inform intervention strategies as Sénégal aims for #malaria elimination!
Check out some of Dr Ndiaye's work in this recent publication: malariajournal.biomedcentral.com/articles/10.11… And more to come in these molecular surveillance studies such as monitoring triple and quadruple Pfdhfr and Pfdhps mutations & K13 mutations (the latter by amplicon sequencing). #GEM2021
The 3rd #GEM2021 talk from Annina Schnoz of @SwissTPH was a brilliant comparison of genotyping methods for differentiating Pf recrudescence from new infections in antimalarial drug clinical trials. Using lab strains 3D7, K1, HB3, & FC27, resistance marker detection was carried..
... out by Bioanalyzer (QIAxcel), capillary electrophoresis (CE) (an Applied Biosystems Analyzer), AmpSeq (MiSeq platform), and qPCR. It appeared that CE and targeted amplicon deep sequencing (AmpSeq) showed the highest sensitivity in detection of clones! #GEM2021
Some brilliant #GEM2021 lightning talks too! Alfred Amambua Ngwa of @mrcunitgambia on monitoring an amino acid transporter in epistasis with CQ resistance markers; Irene Omedo of @malariagenomics on spatio-temporal distribution of antimalarial drug resistance markers in Kenya;...
.. and ending the #GEM2021 Drug Resistance session, Aung Myint Thu of @MORUBKK describing ART-R mutations across Myanmar from 2014-2019 as part of his work on the Malaria Elimination Taskforce (METF). Low prevalence of the C580Y allele (<3%), but an increase in F446I! #malaria
The #GEM2021 Session 4, "Biological Insights from Genomes" was introduced by a talk by @TheBeiLab in using genetic & genomic approaches to inform malaria interventions & vaccine design! Dr Bei cited a nice, recent introduction article to #malaria vaccines: ncbi.nlm.nih.gov/pmc/articles/P…
And then @TheBeiLab moved into a discussion of the PfRh5 invasion complex. What is the extent of natural diversity in PfRh5 and binding partners? (A bit about a binding partner at pubmed.ncbi.nlm.nih.gov/28186186/). And taking findings from genomic data such as in the @malariagenomics..
.. A functional genomic approach could be applied, resulting in identification of the functional impact of Rh5 SNPs! And what you get is @AJMooreHealth et al!: nature.com/articles/s4159… With even more to come from Mangou, Moore, Thiem (in prep!). #GEM2021
After assessing the function of SNPs to vaccine targets such as PfRh5, the 2nd #GEM2021 "Biological Insights" talk was from Gavin Band of @malariagenomics who described how the protective effect of sickle haemoglobin against severe malaria depends on parasite genotype!
So Gavin Band works on the incredible @malariagenomics dataset introduced in nature.com/articles/s4146… (& more besides)! So Dr Band looked at the pairwise association between human blood group variants and Pf variants from severe malaria cases! #GEM2021
Strikingly, 3 areas of the #Plasmodium falciparum genome were associated with severe #malaria in HbS hosts, with an association of SNPs Pfsa1, Pfsa2, and Pfsa3 in the sickle cell allele in instances of severe malaria in these hosts. On @biorxivpreprint at biorxiv.org/content/10.110…
The 3rd #GEM2021 "Biological Insights" talk dealt with a different SNP and a different geographic region! Dr Jonathan Parr (@jonbparr) of @UNC told us about how the Pfhrp2 deletion is under positive selection in Ethiopia, threatening diagnostic & control strategies! #malaria
Citing some great background as published in malariajournal.biomedcentral.com/articles/10.11…, Dr Parr describes the development of new molecular inversion probe (MIP) sequencing method to detect Pfhrp2/3 deletion parasites, revealing distinct subtelomeric structural profiles! #GEM2021
But don't take my word for it! @jonbparr's work that he spoke about today can be found on @medrxivpreprint at medrxiv.org/content/10.110… #GEM2021
For #GEM2021 talk 4 of "Biological Insights", the focus turned to within-host #Plasmodium evolution with Dr Ian Cheeseman (@doubleholliday2) who showed just how much information on parasite lineage/clonality can be gleaned using single-cell sequencing: sciencedirect.com/science/articl…
The publication above describes P. falciparum within-host genetic diversity, but what about vivax? In his #GEM2021 talk, @doubleholliday2 addresses single-cell seq of P. vivax as in Pf, showing de novo mutations in natural P. vivax infections. Sneak peak: papers.ssrn.com/sol3/papers.cf…
The final long talk of #GEM2021 Session 4 was from James Watson of @MORUBKK who discussed "improving statistical power in severe #malaria genetic association studies by augmenting phenotypic precision". Oh excellent! Preprint on @biorxivpreprint at biorxiv.org/content/10.110…
And a few #GEM2021 lightning talk notes: @EsohKevin describes malaria GWAS in Cameroon at nature.com/articles/s4159…, @emilylav described the development & evaluation of 2 new amplicon panels for #Plasmodium falciparum surveillance with the @dneafse Lab;...
@alimanfoo described the new Anopheles gambiae 1000 genomes Project: Phase 3 Data Resource at malariagen.net/ag3 & a new haplotype reference panel in production; & Richard Pearson of @malariagenomics described new data available in the PF7 dataset: malariagen.net/resource/34
Day 3 of #GEM2021 began with the "Bioinformatics Tools for the 21st Century", introduced by a talk from @jeromekelleher of @UniofOxford who discussed "Genealogical trees at the population scale." Dr Kelleher describes the tree sequence framework used in genetics.org/content/215/3/…
Using tree-sequence based analysis to infer descent/genealogy can be used for any recombining organism (incl. #Plasmodium), but @jeromekelleher's latest preprint utilises this method to analyse vast human genome samples at biorxiv.org/content/10.110… #GEM2021
And though this can be quite computational in nature & challenging to grasp for some of us primarily "wet lab" #GEM2021 attendants, @jeromekelleher kindly provided a link to a talk by the preprint's 1st author on "Tree sequence fundamentals" at:
The second #GEM2021 "Bioinformatics" talk was from Marilou Boddé at @Cambridge_Uni & will be coming soon to a paper near you! Marilou described "High resolution Anopheles species assignment from a genus-wide sequencing approach", showing how a targeted amplicon sequencing...
..panel can be used for surveillance of #malaria vector diversity over space and time. Marilou described the development of both top-down and bottom-up hierarchical classifiers trained on amplicon data & in silico amplified samples from the Ag1000G dataset! >98% accuracy in both!
Talk 3 of #GEM2021 Session 5 ("Bioinformatics") was from Inna Gerlovina of @EPPIcenter_UCSF who discussed "Fast estimates of IBD from unphased polyclonal #malaria infections with Dcifer." Dr Gerlovina cited the use of microhaplotypes in discriminating related from non-related...
... P. falciparum samples, as detailed in academic.oup.com/jid/advance-ar… Some more additions to be made to the model, but keep an eye on @innager01 for future updates on Dcifer! #GEM2021 #malaria
Talk 4 of #GEM2021's "Bioinformatics" session was by David Plaza of @karolinskainst, who brought us up to speed on "A genomic surveillance platform for indel-rich genes from #Plasmodium spp. using long-read amplicon sequencing"! Great intro of msp2 cited: journals.plos.org/plosone/articl…
This was all new and cutting-edge work from David Plaza at #GEM2021 in which he described his computational analysis of a circular consensus sequencing (CCS) library for msp2 amplicons (using both direct coding & @galaxyproject). More to come from Dr Plaza linkedin.com/in/david-ferna…
#GEM2021 Bioinformatics lightning talks were then provided by Jacob Almagro Garcia of @bdi_oxford, who introduced the @malariagenomics interactive notebooks & standalone tools (SO MUCH at malariagen.net/resources/data…)! Then @bricoletc at @emblebi described building a "global map...
... of the diversity of #Plasmodium falciparum surface antigens". Check the preprint out at biorxiv.org/content/10.110… And then Kevin Wamae of @UNC (@KevinKariuki) described analyses of antigen variants over time, incl. deep seq of AMA1 & AMA2, and mapping mdr1 variants over time!
So judging from the #GEM2021 "Bioinformatics" session today, we're going to have to keep our eyes peeled for a selection of new software tools, including those from Marilou Boddé at @Cambridge_Uni, @innager01 of @EPPIcenter_UCSF, David Plaza at @karolinskainst, & @KevinKariuki!
Session 6 of #GEM2021 was the longest session of all: "Transmission"! Dr Robert Verity of @imperialcollege began the session with his talk on "SIMPLEGEN: Exploring genetic sampling design through simulation." (SIMPLEGEN = SIMulating PLasmodium Epidemiology & GENetics)!
I love the opensource nature of bioinformatics and epidemiological modelling! SIMPLEGEN is written in R and C++ and you can find it here: mrc-ide.github.io/SIMPLEGEN/ It is currently in developmemt & if you have an epi #Plasmodium model to incorporate, contact Dr Verity & let him know
Talk 2 of the #GEM2021 Transmission session was incredible! Dr Abdoulaye Diabaté of @TargetMalaria discussed "Gene drives for #malaria vector control: from lab to application". If you haven't seen the @TargetMalaria website, you really should check it out: targetmalaria.org/what-we-do/how…
Dr Diabaté went through everything! From the options for genetic control of mosquito-borne infectious diseases to gene drive testing hurdles (incl. public acceptance). From the science & stakeholders, to setting up a Centre of Excellence at the insectary in Burkina Faso! #GEM2021
Dr Diabaté emphasised the importance of engaging with the community about the work of @TargetMalaria & genetically-modified mosquitoes, whether it be a village or the country as a whole. Communication of the science is so important! With the 1st release in 2016; this 2017 paper..
.. describes how the lab then measured the dispersal of the GM mosquitoes & provides an excellent starting point for further field studies in Africa: parasitesandvectors.biomedcentral.com/articles/10.11… Of course, so much more to come from @TargetMalaria in future! #GEM2021
The 3rd "Transmission" talk of #GEM2021 was from Hazel Beverly Gwarinda of @UPTuks who described "#Plasmodium falciparum diversity associated with continued #malaria transmission in pre-elimination settings in South Africa." Hazel's work shows how genomics allows us to assess...
.. transmission through genetic diversity & can be used as a surveillance tool. Her work shows that within-host infections are highly interbred, with population-level genetic diversity displaying allelic richness. Check out recent research at europepmc.org/article/MED/33…
And then on to the #GEM2021 "Transmission" lightning talks! Juliana Cudini of the #malaria Cell Atlas told us about "profiling the sexual development of #Plasmodium falciparum using scRNAseq.": nature.com/articles/s4146… Then @JasonAHendry1 described the development of a genetic-...
..epidemiological model for #malaria by combining the Ross-MacDonald model (epidemiology) with the Moran model (population genetics) to create "forward-dream": biorxiv.org/content/10.110… @MxMur of @EPPIcenter_UCSF then took us through "Inferring transmission dynamics", with some...
..of this cutting-edge work available in preprint form at medrxiv.org/content/10.110… And penultimately, for the #GEM2021 "Transmission" session, @MyoThetNaung of @WEHI_research described "naturally acquired immune responses to #Plasmodium falciparum vaccine antigens with various...
.. levels of genetic diversity". No publication yet, so keep up with @MyoThetNaung for more updates! And the final #GEM2021 "Transmission" talk was from Dr Abebe Fola (@abebe_fola) of @PurdueEEB about "Quantifying #Plasmodium falciparum diversity & relatedness across Zambia and..
... neighbouring countries", where #malaria (Pf) transmission is still endemic to certain regions and highly heterogeneous. But to read more in future on how @abebe_fola determined IBD relatedness & spatial patterns of parasite connectivity across Zambia, follow him! #GEM2021
The final #GEM2021 Session was fascinating. Entitled "Genomic surveillance for Elimination and Barriers to Translation", Dr Sofonias Tessema (@sofoniaskt) of @UCSF and @AfricaCDC started with a discussion of the "Africa Pathogen Genomics Initiative (Africa PGI): Beyond COVID-19."
Citing this excellent paper: thelancet.com/journals/lanin… Dr Tessema tells us that Africa PGI was launched only 2 months before the COVID-19 outbreak, with >80% of NGS capacity in non-public health institutions in Africa. Hopefully, COVID-19 has taught us that this needs to change.
Following this illuminating talk about establishment of Africa PGI & a sequencing revolution in Africa, our second #GEM2021 Session 7 was from @jennifergardy of the @gatesfoundation, who discussed "Advancing genomics for #malaria eradication: what can we learn from COVID-19."
You can find more on Dr Gardy at gatesfoundation.org/about/leadersh… and during #GEM2021, Dr Gardy described the need for post-pandemic uses for sequencing cores; that core sequencing facilities with trained staff & the ability to sequence multiple pathogens are the way forward, as are...
... core staff with the training to quickly troubleshoot upstream reagent acquisition or usage issues, & also those that can manage and analyse the downstream data (she described the sequencing system as a bowtie, with the actual sequencer in the centre but upstream & downsteam..
.. issues at either side!). And as I've heard at #genomics conferences before, data storage & international data sharing are key components in the successful implementation of genomic epidemiology! So after that wonderful talk, the final #GEM2021 presentation was by none other..
.. than Dominic Kwiatkowski of @malariagenomics with "Putting genomic epidemiology into practice for #malaria and COVID-19." Dr Kwiatkowski described how by April 2020, the @sangerinstitute & new Lighthouse Labs in the UK were collaborating to create a systematic framework for..
.. national genomic surveillance of COVID-19. You can, in fact, view the genomes per week sequenced, & the proportion of variants over time, at covid19.sanger.ac.uk/lineages/raw Truly incredible feat! Can you just imagine this type of data for #malaria worldwide or by country in future?!
Dr Kwiatkowski of @malariagenomics at #GEM2021 tells us that this level of longitudinal genomic surveillance over time may seem boring at first, until the unexpected arises, such as the case with COVID-19 variants. Informed #malaria control will need to incorporate genomic...
.. epidemiology in future, as will #malaria elimination strategies. And to end, Dr Kwiatkowski is looking forward to GEM Africa conferences in future! And we must also wish one of @malariagenomics's OG scientists a happy retirement: thank you Dr Kirk Rockett for all you've done!
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