Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches

Machine Learning for Biomedical Literature Triage

This paper presents a machine learning system for supporting the first task of the biological literature manual curation process, called triage. We compare the performance of various classification models, by experimenting with dataset sampling factors and a set of features, as well as three different machine learning algorithms (Naive Bayes, Support Vector Machine and Logistic Model Trees). The results show that the most fitting model to handle the imbalanced datasets of the triage classification task is obtained by using domain relevant features, an under-sampling technique, and the Logistic Model Trees algorithm