Hello there! My name is Frances Hall PhD and I started my career at Instem in the GeneTox Team, enabling CROs, Pharma Companies, Universities and Research Institutes to gain value from the software solutions Instem provides for the genetic toxicology market, such as Comet Assay IV and Cyto Study Manager.

More recently, I’ve been working closely with clients on Target Safety Assessments (TSAs) as part of our KnowledgeScan TSA service team and I’ve learnt two things:

  1. People resonate with visuals in the form of colourful pictures, infographics, charts and graphs.
  2. People appreciate a recently assessed and relatable target example.

So, when it’s time to show an example document, I always pick an engaging target to discuss, and for the purpose of this blog I would like to discuss PLK4 – Polo-like Kinase 4. PLK4 is a great target for us to focus on, we used 72 PLK4 synonyms (alternative target names) and we found over 500 records in PubMed. The KnowledgeScan production team searched across the literature landscape, cross referencing PLK4 publications with our library of organ and adverse outcome terminology, and we identified 32 risks across 23 different organs.

PLK4 has an essential role in centriole duplication. The protein localizes to centrioles and regulates centriole duplication during the cell cycle. PLK4 turn-over must be strictly controlled to prevent centriole amplification. Therefore, PLK4 inhibitors have potential in cancer treatment; rendering cells unstable and more sensitive to chemotherapy. Given the role and cancer-focussed fame of PLK4, you might think that risks were limited to carcinogenesis, cell proliferation and ciliogenesis, however, this was not the case. Although we detected risks in those three areas, the most popular organs for risks were eye and lung.

Within the PLK4 corpus (collection of information), the amount of cancer-related literature does dominate the dataset, but this is a very typical (and real) target. The PLK4 TSA is an excellent discussion starter, where we can talk about how the KnowledgeScan platform handles larger, more complex, more weighted datasets.
Going back to my first point, PLK4 also has some immense Instem-developed infographics. In particular the Expression Topography and the Iris Plot are two excellent examples of how we can display large amounts of information succinctly and beautifully. When viewing the graphics, themes and stories are instantly revealed, and the observer can start asking appropriate questions.

If you’d like to see these PLK4 graphics and more, you can find my poster discussing this target at the upcoming SOT (Society of Toxicology, March 19-23, Nashville, TN, USA) meeting: 3096:202: Polo-like kinase 4 (PLK4) safety review – distilling the risks with a rapid augmented intelligence approach.

Alternatively, email me (frances.hall@instem.com) and I’ll gladly send you a copy.


  1. https://www.instem.com/news/articles/0601-sot-2023-events.php

Published by Glenn Myatt

Glenn J. Myatt is the co-founder of Leadscope and currently Senior Vice President, In Silico & Translational Science Solutions at Instem with over 30 years’ experience in computational chemistry/toxicology. He holds a Bachelor of Science degree in Computing, a Master of Science degree in Artificial Intelligence and a Ph.D. in Chemoinformatics. He has published 37 papers, 11 book chapters and three books.