Cotton Genomics and Genetics 2025, Vol.16, No.5, 210-221 http://cropscipublisher.com/index.php/cgg 218 channel can be opened for the development of new varieties with stress tolerance and high yield (Wen et al., 2023). Sometimes, what is truly useful is not necessarily those conventional genes that are "present in all varieties", but rather these less popular ones, which are more likely to bring about unexpected gains in breeding. 8 Concluding Remarks and Future Perspectives Some questions, in fact, cannot be answered no matter how many times you search the reference genome. It was not until the introduction of the pan-genome that many "invisible corners" began to be illuminated-those missing genes, structural variations, and even brand-new expression patterns gradually emerged. The previously overlooked variations have now become a key breakthrough point, especially in breeding goals such as fiber quality, yield, and stress resistance, where the changes are even more pronounced. But then again, things are not that simple. It is still unclear what exactly those optional genes and private genes that only appear in some materials do at different developmental stages. How subgenomic expression bias is regulated and how multi-omics data are interconnected and connected are still in a semi-solved state at present. Whether the pan-genome can be truly applied in practice depends on whether the technology keeps up. First of all, it is necessary to measure quickly and accurately. This is the foundation. The currently commonly used high-throughput sequencing and assembly technologies capable of handling extremely long fragments still need to be further upgraded in the future. Then, methods that can "see more precisely", such as single-cell omics and spatial omics, should also be accelerated simultaneously. On the other hand, whether it is identifying structural variations (such as large fragment insertions, deletions, inversions), PAVs (presence/absence variations), or finding regulatory elements, if the algorithm is not effective, the efficiency and accuracy will also be compromised. However, to be fair, it is probably difficult to bring the entire system to life with just one or two technological advancements. What we truly need is an open platform similar to a "cotton version of ENCODE", integrating various omics data, regulatory relationships, and functional annotations together. The key point is not to set up a database and leave it untouched, but to make this platform effortless to use-easy to search for information, not difficult to operate, and quick to update. For those engaged in research, breeding, or even in the industrial sector, this kind of thing is not an "added bonus", but an "essential tool". The direction of cotton breeding in the future is likely not to be a single technology going it alone, but rather a combination of several core methods: for instance, the pan-genome can tell you the potential key genes, CRISPR can precisely edit them by hand, and AI algorithms can help you quickly select the optimal combination. Only if this process can run smoothly can there be hope of breeding new cotton varieties that are disease-resistant, high-yielding and have good fiber quality. But to reach that point, it is unrealistic for a single laboratory to go it alone. Cross-disciplinary collaboration, open sharing of research data, and long-term stable resource support are all indispensable. Ultimately, whether cotton can breed the next generation of "super varieties" is not only a matter of agricultural technology, but also closely related to the foundation of sustainable development of food and fibers on a global scale. Acknowledgments I thank the anonymous reviewers for their insightful comments and suggestions that greatly improved the manuscript. Conflict of Interest Disclosure The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Arslan M., Fatima A., Javeria F., Ijaz S., Riaz U., Saleem G., Bekhit M., Mezher M., and Iqbal R., 2025, Assessment of genetic diversity in cotton genotypes using simple sequence repeat (SSR) markers: insights from interspecific and intraspecific variations, Genetic Resources and Crop Evolution, 72(3): 3661-3670. https://doi.org/10.1007/s10722-024-02185-y Bao Y., Hu G., Grover C., Conover J., Yuan D., and Wendel J., 2019, Unraveling cis and trans regulatory evolution during cotton domestication, Nature Communications, 10(1): 5399. https://doi.org/10.1038/s41467-019-13386-w
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