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Credit: Peter H. Seeberger
Researchers have devised a way to perform genome sequencing on individual cells infected with malaria parasites.
The team found this single-cell approach could generate parasite genome sequences directly from the blood of patients infected with Plasmodium vivax or Plasmodium falciparum.
It provided new insight into the biology of the parasites, revealing their virulence and capacity for drug resistance.
The team described this work in Genome Research.
They noted that malaria infections commonly contain complex mixtures of Plasmodium parasites. These multiple-genotype infections (MGIs) can alter the impact of the infection and drive the spread of drug resistance. MGIs are extremely common in regions with high levels of malaria infection, but their biology is poorly understood.
“Up to 70% of infections in sub-Saharan Africa are MGIs, and we currently don’t know how many genotypes are present and whether parasites come from a single mosquito bite or multiple mosquito bites,” said study author Shalini Nair, of Texas Biomedical Research Institute in San Antonio.
“Current sequencing techniques really limit our understanding of malaria parasite biology,” added study author Ian Cheeseman, PhD, also of Texas Biomed.
“It’s like trying to understand human genetics by taking DNA from everyone in a village at once. The data is all jumbled up, but what we really want is information from individuals.”
To achieve a better understanding of MGIs and malaria parasites in general, the researchers developed a method for isolating an individual parasite cell and sequencing its genome. Although single-cell genomics approaches are already used in cancer research, it has been difficult to adapt the approach to other organisms.
“One of the real challenges was learning how to cope with the tiny amounts of DNA involved,” Nair said. “In a single cell, we have a thousand-million-millionth of a gram of DNA. It took a lot of effort before we developed a method where we simply didn’t lose this.”
But the researchers eventually found they could use methods of single-cell sorting and whole-genome amplification to separate out individual cells and amplify their DNA for sequencing. The team sequenced the DNA from red blood cells infected with P falciparum or P vivax.
They discovered this technique can reveal the composition of MGIs and provide information on the strength of an infection and the development of drug resistance.
“One of the major surprises we found when we started looking at individual parasites instead of whole infections was the level of variation in drug-resistance genes,” Nair said. “The patterns we saw suggested that different parasites within a single malaria infection would react very differently to drug treatment.”
Unfortunately, this technology is currently too expensive and demanding for routine use in the clinic. But the potential applications are significant, according to the researchers.
“We’re now able to look at malaria infections with incredible detail,” Dr Cheeseman said. “This will help us understand how to best design drugs and vaccines to tackle this major global killer.” 
Credit: Peter H. Seeberger
Researchers have devised a way to perform genome sequencing on individual cells infected with malaria parasites.
The team found this single-cell approach could generate parasite genome sequences directly from the blood of patients infected with Plasmodium vivax or Plasmodium falciparum.
It provided new insight into the biology of the parasites, revealing their virulence and capacity for drug resistance.
The team described this work in Genome Research.
They noted that malaria infections commonly contain complex mixtures of Plasmodium parasites. These multiple-genotype infections (MGIs) can alter the impact of the infection and drive the spread of drug resistance. MGIs are extremely common in regions with high levels of malaria infection, but their biology is poorly understood.
“Up to 70% of infections in sub-Saharan Africa are MGIs, and we currently don’t know how many genotypes are present and whether parasites come from a single mosquito bite or multiple mosquito bites,” said study author Shalini Nair, of Texas Biomedical Research Institute in San Antonio.
“Current sequencing techniques really limit our understanding of malaria parasite biology,” added study author Ian Cheeseman, PhD, also of Texas Biomed.
“It’s like trying to understand human genetics by taking DNA from everyone in a village at once. The data is all jumbled up, but what we really want is information from individuals.”
To achieve a better understanding of MGIs and malaria parasites in general, the researchers developed a method for isolating an individual parasite cell and sequencing its genome. Although single-cell genomics approaches are already used in cancer research, it has been difficult to adapt the approach to other organisms.
“One of the real challenges was learning how to cope with the tiny amounts of DNA involved,” Nair said. “In a single cell, we have a thousand-million-millionth of a gram of DNA. It took a lot of effort before we developed a method where we simply didn’t lose this.”
But the researchers eventually found they could use methods of single-cell sorting and whole-genome amplification to separate out individual cells and amplify their DNA for sequencing. The team sequenced the DNA from red blood cells infected with P falciparum or P vivax.
They discovered this technique can reveal the composition of MGIs and provide information on the strength of an infection and the development of drug resistance.
“One of the major surprises we found when we started looking at individual parasites instead of whole infections was the level of variation in drug-resistance genes,” Nair said. “The patterns we saw suggested that different parasites within a single malaria infection would react very differently to drug treatment.”
Unfortunately, this technology is currently too expensive and demanding for routine use in the clinic. But the potential applications are significant, according to the researchers.
“We’re now able to look at malaria infections with incredible detail,” Dr Cheeseman said. “This will help us understand how to best design drugs and vaccines to tackle this major global killer.”
Credit: Peter H. Seeberger
Researchers have devised a way to perform genome sequencing on individual cells infected with malaria parasites.
The team found this single-cell approach could generate parasite genome sequences directly from the blood of patients infected with Plasmodium vivax or Plasmodium falciparum.
It provided new insight into the biology of the parasites, revealing their virulence and capacity for drug resistance.
The team described this work in Genome Research.
They noted that malaria infections commonly contain complex mixtures of Plasmodium parasites. These multiple-genotype infections (MGIs) can alter the impact of the infection and drive the spread of drug resistance. MGIs are extremely common in regions with high levels of malaria infection, but their biology is poorly understood.
“Up to 70% of infections in sub-Saharan Africa are MGIs, and we currently don’t know how many genotypes are present and whether parasites come from a single mosquito bite or multiple mosquito bites,” said study author Shalini Nair, of Texas Biomedical Research Institute in San Antonio.
“Current sequencing techniques really limit our understanding of malaria parasite biology,” added study author Ian Cheeseman, PhD, also of Texas Biomed.
“It’s like trying to understand human genetics by taking DNA from everyone in a village at once. The data is all jumbled up, but what we really want is information from individuals.”
To achieve a better understanding of MGIs and malaria parasites in general, the researchers developed a method for isolating an individual parasite cell and sequencing its genome. Although single-cell genomics approaches are already used in cancer research, it has been difficult to adapt the approach to other organisms.
“One of the real challenges was learning how to cope with the tiny amounts of DNA involved,” Nair said. “In a single cell, we have a thousand-million-millionth of a gram of DNA. It took a lot of effort before we developed a method where we simply didn’t lose this.”
But the researchers eventually found they could use methods of single-cell sorting and whole-genome amplification to separate out individual cells and amplify their DNA for sequencing. The team sequenced the DNA from red blood cells infected with P falciparum or P vivax.
They discovered this technique can reveal the composition of MGIs and provide information on the strength of an infection and the development of drug resistance.
“One of the major surprises we found when we started looking at individual parasites instead of whole infections was the level of variation in drug-resistance genes,” Nair said. “The patterns we saw suggested that different parasites within a single malaria infection would react very differently to drug treatment.”
Unfortunately, this technology is currently too expensive and demanding for routine use in the clinic. But the potential applications are significant, according to the researchers.
“We’re now able to look at malaria infections with incredible detail,” Dr Cheeseman said. “This will help us understand how to best design drugs and vaccines to tackle this major global killer.”