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The World Drug Report estimates that 5% of the world’s population uses illicit drugs, leading to staggering costs of more than 190 billion dollars annually in the United States alone (UNODC Report, 2010). Addiction is a life-long affliction manifested by persistent drug-seeking behavior and a high frequency of relapse, with well over half of individuals treated for addiction relapsing and falling back into the torment of drug addiction. There is substantial comorbidity of substance use disorders among people living with human immunodeficiency virus (HIV).

Chronic exposure to opioids, methamphetamine, and/or cocaine can lead to long term changes in brain function and to substance use disorders (SUDs). Many known brain regions are involved in addictive processes including the prefrontal cortex, nucleus accumbens, ventral tegmental area, striatum, insula, amygdala, and hippocampus. Despite great advances in our understanding of molecular pathways and circuits involved in SUDs, there remains limited knowledge concerning 1. the specific types, numbers, and gene expression profiles of cells within these brain regions and 2. how environmental exposures to addictive substances influence the states and functions of these cells.

Despite effective viral suppression with antiretroviral medications, approximately 50% of people living with HIV have persistent neurocognitive deficits, especially in working memory and attention. The biological substrates of persistent neurological injury in people with HIV on treatment remain poorly understood, including detailed identification of specific cell populations in the brain that support viral infection. Moreover, use of addictive substances by people living with HIV has the potential to further diminish immune function and/or exacerbate HIV-related CNS impairment, via a variety of pathways that may include heightened neuroinflammation, synergistic mechanisms of neuronal injury, or vascular impairment. However, little is known about 1. the effects of persistent HIV infection or HIV treatment regimens on specific CNS cell types in key brain regions, 2. the molecular characteristics of CNS cell types that harbor HIV, or 3. how chronic addictive substance use might modify these effects. Single cell technologies have the potential to shed light on these processes.

The NIDA-supported Single Cell Opioid Responses in the Context of HIV (SCORCH) program was established in 2020, with the mission of generating resources that would enable comprehensive tissue characterization at the single-cell level. This includes generating single-nucleus transcriptomic data for the identification of novel rare cell types, and enrichment of key cellular populations to inform pathophysiological understanding of CNS effects of SUD and HIV.

The SCORCH data coordination, analysis, and scientific outreach center will be established to standardize and share single cell molecular HIV/SUD data generated by this program by ensuring that the data is FAIR (Findable, Accessible, Interoperable, and Reusable). The SCORCH Data Center will also integrate other molecular HIV/SUD data sets generated by NIDA-funded investigators to maximize their value to the scientific community. This data center is expected to leverage knowledge and resources generated by BICCN, HuBMAP, and other single cell initiatives to maximize scientific understanding. Harmonized molecular and single cell HIV/SUD data sets will enable near term data mining by the scientific community to identify HIV and/or SUD biomarkers and identify candidate pathways for therapeutic intervention. The SCORCH Data Center will also enable future mining of these data sets as new and improved data science and information technology approaches are developed, maximizing NIDA’s original investment in the data generating activities.

SCORCH is an interdisciplinary effort, involving teams of investigators at nine institutions – Yale, the J. Craig Venter Institute and Boston University and Mount Sinai, the University of Nebraska Medical Center, the Broad Institute, University of California San Diego and Weill Cornell Medicine, as well as a Data Coordination Center (DCC) hosted at the Institute for Genome Sciences, University of Maryland Baltimore School of Medicine.

References:
RFA-DA-20-027
RFA-DA-19-038

Memberships
Broad Institute
Yale School of Medicine
The Institute for Genome Sciences
J. Craig Venter Institute
ICAHN School of Medicine at Mount Sinai
University of Nebraska Medical Center
University of California San Diego
Weill Cornell Medicine