Drug Signatures for Prediction and Mitigation of Toxicity

The overall goal of the drug signatures for prediction and mitigation of toxicity study is to use genomic and proteomic high-throughput measurements as the basis for computational analysis that integrates network analyses with structural constraints and dynamical models in multiple cell types to identify signatures that predict toxicity induced by 55 FDA-approved chemotherapeutic drugs and potential mitigation of this toxicity.

Specifically, we have recruited and pre-screened healthy individuals to be included in our study. Ninety six male and female individuals that satisfied the initial pre-screening for the study and their sex, age, race/ethnicity recorded through an enrollment questionnaire were consented. Eighty five underwent a formal and thorough medical health screening. The evaluation involved assessment of all inclusion and exclusion criteria, a full medical history, measurement of weight, height, waist and hip circumference, heart rate, blood pressure, respiratory rate, and oxygen saturation, a physical exam and an electrocardiograph (ECG). Blood was drawn for analysis of clinical relevant parameters. A pregnancy test was included for female participants. All blood draws and pregnancy tests were sent to a certified clinical laboratory for clinical analysis. Of the 85 subjects that were screened 42 (48.3%) were deemed eligible for final inclusion. Of these 42, one declined to undergo skin biopsy and/or venesection and one subject didn't show up for the scheduled biopsy, leaving 40 clinically healthy subjects on which a skin biopsy and venesection was performed.

Fibroblast lines were established from the skin biopsies. Induced pluripotent cells (iPSC) were generated from the established fibroblast lines of these 40 clinically healthy racially diverse male and female study participants who ranged in age from 22 and 61 years through reprogramming using either the mRNA or Sendai-virus methods. One clone from each of the 40 iPSC line was fully characterized for normal karyotype, short-tandem repeat matching to the original fibroblast line (authentication), pluripotency by select pluripotent marker expression via immunocytochemistry and by mRNAseq-based PluriTest analysis, and whole-genome sequencing.

• Study Design:
  • Control Set
• Study Type:
  • Control Set
• Total number of consented subjects: 40
• Subject Sample Telemetry Report (SSTR)

• BioProject
• Sequence Read Archive
• BioSample
• GEO

Any individual between the ages of 18-65 if s/he fulfilled the following inclusion/exclusion criteria.

Inclusion Criteria:

• Any healthy individual with no diagnosed disorder/disease or condition requiring hospitalization or immune suppression.

• Any healthy individual not taking any prescription medication

• For skin biopsy: Any individual whose tests/procedures as detailed in the CRC application are within a normal/reference range or otherwise normal, including normal ECG parameters such as normal heart beating rate, normal rhythm, normal voltage, etc.

Exclusion criteria:

• Any individual with a diagnosed disorder/disease.

• Any individual who has a family history of disease/illness/disorder

• For skin biopsy: Any individual who does not fulfill the inclusion criteria, specifically any individual with any health check parameter outside the respective normal/reference range or an abnormal ECG, including individuals positive for HIV or individuals who are pregnant.

• Primary Phenotype: Drug-Related Side Effects and Adverse Reactions

• Principal Investigator
  • Srinivas (Ravi) Iyengar, PhD. Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• Funding Source
  • U54 HG008098. National Institutes of Health, Bethesda, MD, USA.