Demichelis Lab - Computational Oncology

Translational research hinges on the ability to make observations in model systems and to implement those findings into clinical applications, such as the development of diagnostic tools or targeted therapeutics. Tumor cell lines are commonly used to model carcinogenesis. The same tumor cell line can be simultaneously studied in multiple research laboratories throughout the world, theoretically generating results that are directly comparable. One important assumption in this paradigm is that researchers are working with the same cells. However, recent work using high throughput genomic analyses questions the accuracy of this assumption. Observations by our group and others suggest that experiments reported in the scientific literature may contain pre-analytic errors due to inaccurate identities of the cell lines employed. To address this problem, we developed a simple approach that enables an accurate determination of cell line and sample identity. We described (Demichelis F, et al, Nucleic Acids Research, 2010) the empirical development of a SNP panel identification assay (SPIA) compatible with routine use in the laboratory setting to ensure the identity of tumor cell lines and human tumor samples throughout the course of long term research use.

Schematic illustration of probabilistic test settings. The figure shows the binomial distributions of real match pair population (red dots) and of non-pair population (blue dots) for N equal to 30 and PM and Pnon-M, for the real match pair population and the non-pair population, equal to 0.9 and 0.4. The red, blue and green bars define regions of ‘different’ (mnon-M set equal to 1), ‘uncertain’ and ‘similar’ (mM set equal to 2) SPIA test calls. The smaller the number of SNPs is, the narrower the region of uncertainty and the higher the probability of making an incorrect call.

Schema of SNP panel identification assay (SPIA) applicability and use modality.

• R Library available at CRAN
• Reference Manual
• Original Manuscriptnar_2008-demichelis-2446-56-1.pdf