How Open-Source Science Is Fighting Back Against Pathogens
When the global mpox outbreak emerged in 2022, health officials faced critical questions: Was this a new virus? How was it spreading? Why did it behave differently than previous outbreaks? The answers lay hidden in the virus's genetic code—and scientists used open-source bioinformatics tools to decode them.
Viruses are masters of evolution, constantly changing their genetic makeup to adapt and survive. The Monkeypox virus (MPXV), like other viruses, contains all its instructions in a DNA genome that it hijacks our cells to replicate. Understanding these instructions—the genetic code—gives us powerful insights into how viruses work, how they spread, and how to stop them. Thanks to revolutionary advances in sequencing technologies and the development of freely available bioinformatics software, scientists can now read viral genomes with unprecedented speed and precision, transforming our ability to track and respond to infectious disease threats 2 4 .
Viruses mutate rapidly, creating new variants that can evade immunity and spread more efficiently.
Freely available bioinformatics software enables researchers worldwide to analyze viral genomes.
The journey of viral genome sequencing began modestly. In 1977, scientists sequenced the first DNA genome—Bacteriophage φX174, containing just 5,368 base pairs (the building blocks of DNA) 2 . This breakthrough required painstaking laboratory work. Today, modern sequencing platforms can generate entire viral genomes in hours, creating a deluge of data that would be impossible to analyze without sophisticated computational tools.
Scientists now have multiple powerful methods for reading viral genomes:
| Technology | Max Read Length | Key Advantages | Best For |
|---|---|---|---|
| Illumina | 2×300 bp | High accuracy (99.9%), cost-effective | Variant detection, outbreak tracking |
| Nanopore | Up to 4 Mb | Portable, real-time analysis, detects DNA modifications | Field sequencing, rapid response |
| SMRT-seq | Up to 100 kb | Very long reads, detects DNA modifications | Complex genomic regions, new viruses |
Each technology has strengths that make it suitable for different scenarios. Illumina systems excel at accurately reading short segments, making them ideal for detecting small mutations. Nanopore sequencing, notably used in portable devices like the MinION, allows scientists to sequence viruses in real-time, even in field laboratories during outbreaks 2 . This portability proved invaluable during the Ebola outbreak in West Africa and more recently for mpox surveillance.
When mpox began appearing unexpectedly in multiple countries in 2022, scientists quickly sequenced the viruses to understand what was happening. A crucial study conducted in Italy provides a fascinating window into how genomic detective work helps us understand viral spread 7 .
Researchers analyzed eleven mpox samples collected from patients in the Emilia-Romagna region between May and September 2022. Using whole-genome sequencing and sophisticated phylogenetic analysis (which reconstructs the "family tree" of virus samples), they made a crucial discovery: most samples from male patients clustered with the known circulating strain (lineage B.1), but one sample from a female patient, linked to travel from Ghana, belonged to a different genetic lineage (A.2.3) 7 . This finding demonstrated that multiple introduction events were occurring, not just a single source.
The researchers followed a meticulous process to unravel the mpox genetic code:
Swabs from skin lesions were collected from patients with confirmed mpox infection.
DNA was carefully extracted from the viral particles in these samples.
Using advanced sequencing platforms, the complete genetic code of each virus was read, generating millions of short DNA sequences.
Bioinformatics tools assembled these short sequences into complete viral genomes, like solving a gigantic jigsaw puzzle.
Specialized software identified differences between the sequenced genomes and reference sequences.
Phylogenetic trees were constructed to visualize how the different virus samples were related evolutionarily.
The team specifically looked for a type of mutation caused by human immune system enzymes (APOBEC3), which provides evidence of how long the virus has been adapting to human hosts 7 .
The Italian study revealed several critical findings about mpox evolution:
| Genetic Feature | Discovery | Scientific Significance |
|---|---|---|
| Co-circulating Lineages | Both B.1 and A.2.3 lineages detected | Demonstrated multiple independent introductions |
| APOBEC3 Mutations | Increased G-to-A mutations in human-transmitted viruses | Evidence of human immune system pressure driving evolution |
| Protein Disruptions | Truncations in OPG023 and OPG176 genes | Possible human adaptation through gene inactivation |
| SNP Accumulation | 36 unique polymorphisms in A.2.3 lineage | Genetic diversity enabling tracking of transmission chains |
Perhaps most intriguing was the discovery that viruses circulating in humans showed a distinctive genetic signature of interaction with our immune systems. Our cells produce APOBEC3 enzymes that fight viruses by causing specific types of mutations (changing G nucleotides to A). The researchers found that mpox viruses from the 2022 outbreak had significantly more of these mutations than historical samples, providing clear evidence that the virus had been circulating and adapting in humans 7 .
| Viral Lineage | Average APOBEC-style Mutations | Time Period | Interpretation |
|---|---|---|---|
| Early MPXV | 5-15 | 2017-2020 | Limited human adaptation |
| A.2/A.3 | 16-35 | 2021-2024 | Sustained human transmission |
| A.2.3 | 56.3 (±15.7) | 2022 outbreak | Active human immune pressure |
These genetic clues helped explain why the virus was behaving differently than in previous outbreaks—it had gained mutations that potentially made it better adapted to spread among humans.
The mpox study, like much of modern virology, relied heavily on freely available bioinformatics tools that form the backbone of genomic analysis. These powerful programs help scientists transform raw genetic data into meaningful biological insights.
Rapidly assigns viral sequences to genetic lineages
Lineage AssignmentVisualizes mutations across viral genomes
VisualizationMaps virus-host protein interactions
Network AnalysisDevelops diagnostic tests and research tools
Gene EditingTracks SARS-CoV-2 and other virus variants
Variant TrackingThese tools exemplify the collaborative spirit of modern science. For instance, Jalview allows researchers to visually compare viral sequences from different outbreaks, identifying conserved regions (which make good drug targets) and variable regions (which help track spread) 6 . Cytoscape helps map the complex interactions between viral proteins and our own cellular machinery, revealing vulnerabilities that might be targeted therapeutically 8 .
The CRISPR-Cas9 system, famously adapted from a bacterial immune mechanism, has spawned numerous bioinformatics tools that help design guide RNAs for targeting specific viral genetic sequences 1 5 9 . While CRISPR is best known for its gene-editing applications, in viral genomics, it enables the development of highly specific diagnostic tests and research tools for studying how viruses interact with host cells.
Specialized visualization tools like CoVizu, developed during the COVID-19 pandemic, create intuitive graphical representations of how viral variants are related and how they spread through populations 3 . These visualizations help public health officials and the public understand complex epidemiological patterns without requiring advanced training in bioinformatics.
The ability to rapidly sequence and analyze viral genomes has fundamentally transformed our approach to infectious diseases. We've moved from reacting to outbreaks after they've spread to tracking viral evolution in near real-time, potentially stopping pandemics before they start. The open-source nature of the bioinformatics tools driving this revolution means that researchers worldwide—regardless of their funding resources—can contribute to and benefit from our collective knowledge.
Open-source tools enable scientists in resource-limited settings to participate in global genomic surveillance efforts.
Real-time sequencing and analysis capabilities allow for faster identification of emerging threats.
As sequencing technologies continue to advance and become even more accessible, we're approaching a future where every local public health department could have the capability to sequence viral genomes from patient samples. Combined with the global sharing of genomic data through platforms like GISAID, this creates an unprecedented early warning system for emerging threats.
The genetic code of viruses, once an impenetrable mystery, is now an open book that we're learning to read. With powerful open-source bioinformatics tools as our guide, we're not just cracking the genetic code of human viruses—we're using that knowledge to protect global health in an increasingly interconnected world.