Systems Biology Workgroup

///Systems Biology Workgroup
Systems Biology Workgroup 2021-07-07T16:09:08+00:00

Group Leaders: Dr. Nikolaos Daskalakis, M.D. Ph.D., Dr. Shareefa Dalvie, Ph.D. and Alison Ashley-Koch Ph.D.

Reductionist unimodal techniques did not have substantial success in identifying causal mechanisms for PTSD. There is a need for a more integrated multimodal approach to study the complex interplay between biological and phenotypic constructs.

We aim to delineate complex processes underlying PTSD using a systems biology approach by integrating biological and phenotypic “layers”.

As of 2021, the Systems Biology workgroup has merged with the Gene Expression workgroup, whose goal is to identify the genes that are differentially expressed in controls and individuals with current PTSD. The full PGC- PTSD consortium will generate gene expression data on several thousand individuals, greatly improving power. This data set can be also used in conjunction with multiple other types of ‘omics data, including DNA methylation and genome wide genotype data. This will allow multiple cross-platform analyses to be performed. For example, we will have sufficient power to conduct eQTL analyses to identify genetic variants that can alter the level of expression of specific genes. Likewise, we will be able to identify DNA methylation patterns that may be giving rise to altered gene expression. Such joint analyses of multiple –omics datasets have been previously termed “genomic convergence” and have great potential to inform us about the genetic architecture of PTSD. The working group has several challenges to consider. First, multiple platforms have been used for gene expression analysis—Affymetrix arrays, Illumina arrays, and RNAseq. Combining these data into a single analysis will require the development of new methods. Further, so expression datasets will not have associated GWAS or methylation data, making it harder to correct for population structure and cell type composition of blood samples. The working group will use multiple approaches to address these challenges.

Dr. Nikolaos Daskalakis, MD, PhD

Dr. Daskalakis, MD, PhD, is an associate neuroscientist at McLean Hospital and member of the faculty of Psychiatry at Harvard Medical School. He is also director of Data-science and Translational-medicine. He has received several young investigator awards including the 2015 BBRF-NARSAD Young Investigator and 2018 Brooking Mental Health Research Scholar. He received his MD from University of Athens, his PhD in neuropsychopharmacology from Leiden University, and completed post-doctoral fellowships in clinical neuroendocrinology at Leiden University Medical Center and in molecular psychiatry/bioinformatics at Icahn School of Medicine.

Dr.Daskalakis’ research focuses on the interaction between stress and the brain in health and disease, conducting translational studies in humans and animals following an integrative systems approach. He uses whole tissue and cell type specific RNA sequencing and epigenetic profiling, from the brain, induced neuronal cells, and blood, to identify gene pathways and networks associated with vulnerability and resilience to PTSD. As a member of the Psychiatric Genomic Consortium PTSD Workgroup, Dr. Daskalakis leads large-scale genetic-based analyses and the Systems Biology working group.

Alison Ashley-Koch, Ph.D.

Dr. Ashley-Koch is a Professor in the Duke Molecular Physiology Institute at Duke University Medical Center. She received her PhD in Genetics and Molecular Biology from Emory University and performed postdoctoral training at the Centers for Disease Control and Prevention and Duke University Medical Center. Dr. Ashley-Koch is a genetic epidemiologist whose primary goal is the identification of genetic and genomic risk factors that contribute to a variety of human phenotypes, with a focus on psychiatric traits. Dr. Ashley-Koch performs genetic and genomic analysis of PTSD in military cohorts, including the VA Mid-Atlantic MIRECC and the InTrust data sets. She is also a member of the PsychENCODE project, which uses state of the art molecular tools to characterize genetic regulatory elements in brain tissues and cells. Dr. Ashley-Koch is a co-leader of the PGC-PTSD gene expression working group.

Dr. Shareefa Dalvie, PhD

Dr. Dalvie, PhD, is a faculty member at the Department of Psychiatry & Mental Health at the University of Cape Town (UCT) in South Africa and co-heads the Psychiatric Neurogenetics group of the Brain-Behaviour Unit (BBU) at UCT. She completed her doctoral degree at the Division of Human Genetics at UCT and held a Brain-Behaviour Initiative (BBI) postdoctoral fellowship from the Department of Psychiatry & Mental Health. Dr Dalvie’s research interests include the genetic basis of trauma exposure in individuals with post-traumatic stress disorder (PTSD), network analysis for PTSD integrating “omic” layers, and gene-imaging analysis. Dr Dalvie is also a visiting scholar at the University of California, San Diego (UCSD) in the USA and co-leads the Systems Biology working group of the Psychiatric Genomics Consortium (PGC)-PTSD. She is also a Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER) research fellow (Stanley Center for Psychiatric Research and Harvard T. H. Chan School of Public Health, USA).