Solving the Hard Genomes

Some genomes make you work for them.

They are too large, too repetitive, too degraded, too polyploid, or simply too poorly understood to move smoothly through a standard sequencing pipeline. They challenge researchers at every stage—from sample collection and DNA extraction to sequencing, assembly, curation, and annotation.

Yet these difficult genomes are also where the field advances most rapidly. In this Q&A, experts from across the Earth BioGenome Project network reflect on the challenges, setbacks, and breakthroughs that are expanding the limits of biodiversity genomics. Together, their perspectives reveal how persistence, collaboration, and innovation are transforming today's hardest genomes into tomorrow's routine workflows.

🌍 EBP experts answer the tough questions

Explore expert insights by clicking an image or link below.


What Makes a Genome Hard?

Failure, Persistence, and Breakthroughs

The role of global collaboration

The Next Genomic Frontier


A Global Path Forward

The stories in this issue remind us that every difficult genome solved expands what is possible for the next. Each technical breakthrough, shared protocol, and international collaboration strengthens the foundation for sequencing biodiversity at ever greater scale. As the Earth BioGenome Project enters its next phase, success will be measured not only by the number of genomes produced, but also by how effectively knowledge is shared, methods are refined, and innovations are adopted across the global community. Together, these collective efforts are bringing us closer to the vision of sequencing all known eukaryotic life.

Compiled by: Dr. Anna Bramucci (Earth BioGenome Project: Communications Lead)

Acknowledgements

This special Q&A was made possible by the generosity of researchers from across the Earth BioGenome Project community who took the time to share their experiences, insights, and perspectives. We sincerely thank all of the contributors and Executive Council members whose expertise helped shape this issue. Their reflections highlight not only the technical challenges of sequencing Earth's biodiversity, but also the collaboration, innovation, and persistence that continue to drive the field forward. Together, they embody the spirit of the Earth BioGenome Project: a global community working toward a shared vision of sequencing and understanding all known eukaryotic life.

Harris Lewin