Internship proposal – Genmab BV, Utrecht, NL

Finding co-expressed drug target proteins using single cell RNA sequencing data

Keywords: single cell RNA sequencing, co-expression, cancer, antibody drugs

Duration: 6-9 months

Introduction
Antibody drugs have significantly evolved over the years to complex engineered protein products that have a wide
scope in targeting proteins and eliciting an anti-tumor effect. With the advent of antibody-based drug products that need
to bind two (or more) target proteins to induce their effect, the target space has exponentially grown as we need to
account for the combined expression of targets in cell populations of interest.

In order to identify pairs or even triplets of targets on a given cell, we need to understand their expression, and more
importantly, their co-expression at a single cell level. Single cell RNA sequencing (scRNA-Seq) has rapidly evolved as
a technology that is capable of identifying expression of genes at a single cell level on increasingly large populations
of cells. However, scRNA-seq suffers from stochastic drop-out of measurements which hampers traditional methods of
determining co-expression of genes. This internship will focus on identifying currently available methods to find co-
expressed genes in single cell data, as well as improving existing algorithms to do so. Finally, the intern will apply the
selected and improved approach to identify viable pairs of genes to target with antibody drugs.

An internship at Genmab will give you the opportunity to experience work at a world-class biotech company from early
discovery to full clinical stage projects. You will work with industry scientists, contribute to new drugs in development
and will be able to learn about other exciting ongoing projects.

Goals
Perform a literature study to identify current co-expression methods in single cell RNA sequencing. Apply and
benchmark chosen methods, identify areas of algorithmic improvement. Apply the chosen and improved method on
public and internal scRNA to identify new targets for antibody drugs. Work with drug development scientists to identify
opportunities for follow up studies on these targets. The internship should be concluded with a written report and an
internal presentation for the data science department and the new antibody products team.

Overview of work
 Literature study of available methods for single cell co-expression.
 Working with state-of-the-art infrastructure (Databricks, Amazon Cloud).
 Algorithmic/statistical development/improvement.
 Apply method on public and internal scRNA sequencing datasets.
 Use a combination of reports and dashboards to communicate results of the analyses within Genmab.
 Work with in-house groups to design experiments to validate identified targets.

Candidate profile
 Interested in single cell RNA sequencing data.
 Background in data science, computational biology, machine learning or bioinformatics.
 Affinity with molecular biology and oncology.
 Experience working in R, Python and Unix.
 Motivated by drug development and innovation in biotechnology.