Abstract A016: Companion Diagnostics (CDx) to identify hallmarks of Alternative Lengthening of Telomeres (ALT)
Bibliographic record
Abstract
Abstract Maintenance of telomeres in the absence of telomerase is known as Alternative Lengthening of Telomeres (ALT), which is prevalent in 10-15% of all cancers. Tessellate BIO targets ALT mechanisms to drive cell death by synthetic lethality. To identify patients who will benefit from our therapy, we are developing companion diagnostics (CDx). In this study, established hallmarks of ALT are investigated as CDx target in tissue-derived samples. In fresh and FFPE tumor tissue, presence and abundance of different ALT hallmarks were measured, including RPA phosphorylation, C-circles and telomeric single stranded DNA. While not all markers pass the stringent requirements of a CDx, C-circles prove to be a reliable biomarker. To measure C-circles, a robust and scalable PCR-based protocol was developed, facilitating easy implementation in the clinic. Utilizing this protocol, C-circles were successfully measured across different tissue types. Further, the protocol allowed for C-circle quantification in cell lines, showcasing its utility across matrices of varying complexity. Successful development of the C-circle CDx enables patients selection based on ALT mechanisms herewith improving the response rate of targeted therapies in patients and accelerating new discoveries in the ALT space. Citation Format: Ganesh Kadamur, Dalia Tarantino, Freddie Grogono, Patrick Von Morgen, Salvina Tammaccaro, Diana Zatreanu, Donata Federici Canova, Jana Wolf, Corne van den Kieboom, Katie Chapman, Joris Schuurmans, Jurgen Moll. Companion Diagnostics (CDx) to identify hallmarks of Alternative Lengthening of Telomeres (ALT) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A016.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.028 | 0.012 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".