Several of YSM’s core research facilities utilize state-of-the-art technologies to generate data that shed light on human diseases. YCCI helps support these facilities and the underlying informatics resources and expertise necessary to manage and analyze the data they generate.
At the Yale Center for Genome Analysis (YCGA), James Knight, PhD, research scientist in genetics, leads the development of new analytical tools and pipelines for exome sequencing, transcriptome analysis, and interfacing with clinical studies. Hadoop, the data management system, compresses and stores sequencing data, which are placed in Yale’s Helix data warehouse for clinical use and comparison with other databases. Knight is working with colleagues at Yale Cancer Center, for example, to match variant data from tumor profiling with laboratory and pathology data.
“From a research perspective, clinicians are interested in variant data,” noted Shrikant Mane, PhD, director of the Yale Center for Genome Analysis. One early example that laid the groundwork for this concept involved three members of a family in which whole-exome sequencing revealed a genetic mutation causing an illness that had never been described before. As a result, YCCI, YSM, and Yale-New Haven Hospital established a program to sequence the exomes of children and adolescents with unexplained illnesses. More broadly, the availability of genomic information will allow clinicians to mine these data in order to identify proactively disease-causing variants in clinical situations.
The emerging CyTOF (cytometry by time-of-flight) Core is an exciting new technology for cell analysis that overcomes many of the limitations of flow cytometry; it is another illustration of the marriage of informatics and core technologies. CyTOF uses heavy metal ions as labels combined with mass spectrometry to analyze complex human cell samples, providing more than 40 crystal-clear markers in samples as small as 1,000 cells. Yale’s highly ranked immunology department and cancer research community are utilizing CyTOF to explore numerous conditions in which modulating the immune system may offer better treatments.
“Several generations ago, you measured one thing and you could keep track of it yourself, but we can’t do that anymore,” said Montgomery. “The problems are so big, and the methods of study have become so complex, we have to bring in another element, but we can make more progress.”
Ruth Montgomery, PhD, associate professor of medicine (rheumatology) and associate dean for scientific affairs
CyTOF allows investigators to obtain an unprecedented level of detail about cells, generating complex data that have required a new field of computational analysis. “The data is now so high-throughput that it’s beyond routine analysis,” said CyTOF director Ruth Montgomery, PhD, associate professor of medicine (rheumatology) and associate dean for scientific affairs, who has used CyTOF to show the diversity of natural killer cell responses in West Nile virus infections.
The massive data sets generated by CyTOF, exome sequencing, and other core technologies have required new bioinformatics-based approaches and collaborations. “Several generations ago, you measured one thing and you could keep track of it yourself, but we can’t do that anymore,” said Montgomery. “The problems are so big, and the methods of study have become so complex, we have to bring in another element, but we can make more progress.”