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Outcomes Research
Amplifying the Invisible: Unlocking Genomes That Matter
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In the evolving world of genomic science, a new frontier is being shaped, not in vast DNA libraries or industrial-scale sequencing, but in the careful amplification of life’s tiniest traces.
At the forefront of this movement is Rodrigo de Paula Baptista, PhD, Assistant Research Professor of Medicine and a leading innovator in the use of multiple displacement amplification (MDA) to enable genome sequencing of low-input and hard-to-culture pathogens.
While much of modern sequencing depends on having ample, high-quality DNA, many organisms that pose serious health threats such as Cryptosporidium, Candida auris (now Candidozyma auris based on its recent reclassification to a different genus), and Mycobacterium leprae simply won’t cooperate. They grow poorly in lab cultures, yield scant DNA or come from degraded clinical samples. This is where de Paula Baptista’s research shines.
“MDA allows us to work with precious, degraded or minuscule samples that were once considered unusable for high-resolution sequencing,” said de Paula Baptista. “This is especially impactful in urgent clinical scenarios or in global health settings where pathogens remain underrepresented in public databases.”
A Landmark Study: Making More from Less
In a recent publication, the team demonstrated how MDA—combined with Oxford Nanopore’s long-read sequencing—enables complete genome assembly from DNA inputs far below traditional thresholds. Starting with less than a single cell’s worth of DNA, the team was able to generate contiguous or chromosomal-level assemblies of bacterial and protozoan genomes.
To solve the persistent challenge of chimeric artifacts generated during MDA, the team also developed CADECT (Concatemer Detection Tool)—a custom bioinformatics pipeline that automatically detects and removes problematic reads, thereby improving genome contiguity and fidelity. This innovation not only salvages compromised samples but also opens new possibilities for studying rare pathogens, complex microbiomes, or archived samples with limited material.
MDA allows us to work with precious, degraded or minuscule samples that were once considered unusable for high-resolution sequencing. This is especially impactful in urgent clinical scenarios or in global health settings where pathogens remain underrepresented in public databases.
Rodrigo de Paula Baptista, PhD
Assistant Research Professor of Medicine
MDA: The Backbone of a Broader Research Vision
This study is just one part of a much larger effort led by de Paula Baptista, whose lab is integrating MDA into a diverse suite of global health, clinical, and computational research programs.
“We’re actively applying MDA across several ongoing projects involving pathogens that are hard to grow or yield very little DNA,” he explained. “This includes slow-growing bacteria, fungi like Candidozyma auris, and a range of eukaryotic parasites relevant to global infectious diseases.”
MDA has become a game-changer in clinical scenarios, where timely genome sequencing can mean the difference between a targeted treatment and a missed diagnosis. In particular, the team has used MDA to rapidly amplify DNA directly from patient samples, speeding up antimicrobial resistance (AMR) profiling and improving clinical outcomes.
In addition, this method is being adapted for single-cell genomics, enabling researchers to study intra-host diversity, mixed infections, and even strain switching— factors critical for understanding disease progression, immune evasion, and treatment resistance.
Applications in Global and Clinical Health
de Paula Baptista’s program is particularly tuned to the needs of low-resource settings, where diagnostic tools are often constrained by sample quality and availability. For instance, Candidozyma auris, a multidrug-resistant fungus causing global outbreaks, presents significant challenges for genomic surveillance due to its tough cell wall and low DNA yield.
MDA now allows the team to sequence its genome from minimal input, expediting workflows without compromising quality.
“We’re able to perform whole-genome sequencing on organisms that would otherwise require multiple extractions,” de Paula Baptista noted. “This saves time, resources, and could help hospitals contain outbreaks more quickly.”
Building a Full-Stack Genomics Ecosystem
The team’s innovations don’t stop at the lab bench.
They are building a comprehensive genomic ecosystem that spans from amplification to analysis. Alongside CADECT, the team is developing tools for phenotype classification, high-resolution strain typing and detection of mixed infections. These computational frameworks help researchers extract meaningful biological insights from complex, noisy sequencing data.
The team is also contributing to federal collaborations with the NIH and USDA to expand the genomic representation of poorly characterized or novel microbes, some of which are foodborne or agents of mucosal infections. Their work makes genomics more inclusive. Many of the organisms they study are overlooked, but matter, especially in places where public health infrastructures are under strain.
What’s Next?
With support from federal funding and institutional collaboration, the lab’s future is aimed squarely at tackling hard genomic problems involving low-abundance pathogens, complex infection environments and underserved populations. The integration of MDA with real-time nanopore sequencing, coupled with automated data refinement tools, sets the stage for next-generation precision diagnostics, from the ICU to remote field labs.
“We’re not just trying to sequence genomes,” said de Paula Baptista. “We’re trying to expand the toolbox for infectious disease research and make sure no pathogen goes unstudied just because it’s difficult to work with.”
H. Lander, PhD
August 2025
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