A Difficult Case: What the Diagnostics of Tomorrow Will Look Like

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We have all learned: “Common things are common, except when the diagnosis is rare.” So far so good. Thanks to the large number of cases with increasingly networked data and by taking the current WHO classification as a basis, it is possible for even rare diagnoses to be assigned with greater precision today. This becomes more difficult, however, if the individual findings of the diagnostics chain and the blood values do not fit together in a conclusive way – or if any uncertainty simply remains even though the patient is definitely clinically ill. So what is the next step?

It is precisely here where MLL’s collaboration with Illumina® starts: with our new research project SIRIUS (Solving Riddles Through Sequencing). In this prospective study, which was recently accepted in American study register NCT (NCT05046444), we want to investigate the extent to which a precise genomic and transcriptomic profile (whole genome and whole transcriptome sequencing, WGS, WTS) helps to provide the most likely diagnosis in a complicated case.

As a run-up to this, not only have thousands of hematological diseases been diagnosed according to the latest scientific findings and the data saved at MLL over the last 16 years, but 5,500 genomes and transcriptomes of 30 different diagnoses have been sequenced in the last four years as well. All of this data is now available as a basis for the SIRIUS study.

The study protocol specifies that “difficult cases” be studied in parallel with today’s WHO/Onkopedia gold standard and simultaneously with WGS and WTS. The genomic profile is then compared with all 5,500 profiles of our collection in order to identify the “closest neighbor.” We also expect that good clinical annotation will provide us with valuable information. The ultimate goal is not only to arrive at the best possible diagnosis but possibly the indication of a specific therapy as well. As always, we will determine the precise costs for rendering these services in addition to the time needed to obtain the findings in each instance. In close consultation with the clinical colleagues who have sent us the material, we will then attempt to identify the findings and make patient-related decisions.

So where does the study name SIRIUS come from, you ask? Like the ancient mariners who sailed all over the world using only a sextant and the stars, we now want to use SIRIUS (the brightest star in the night sky) for orientation concerning what diagnostics will look like in the near future.