When is the best time contact a bioinformatician for an NGS study?

a) Before planning the study

b) Before starting the study

c) During the study

d) When the data is generated

Recently, I directed the following question to NGS experimental biologists in a LinkedIn a poll:

When doing an NGS experiment/study, at what stage do you usually reach out to a bioinformatician?

Many thanks to the scientists who voted. The results are as follows:

Before planning the study: 45%

Before starting the study: 21%

During the study: 5%

When the data is generated: 29%

You can find the poll here. Apparently, most of the biologists reach out to a bioinformatician before planning the study, which is good news. As a bioinformatician myself, I am often approached by physicians and life science researchers for bioinformatics assistance with NGS studies. I can provide analytical help at any stage of an NGS study. However, based on my observation, the maximum benefit for the study is obtained when the first contact is made before any work is started.

For an NGS study (whether bulk or single-cell, short- or long-read sequencing), the final product is the information and insights obtained from the generated data. Therefore, generating data that truly serves the ultimate purpose of the study is of utmost importance. That’s why, when planning the experiment, it is vital to consider the end data and the analytical steps. The best way to achieve this is to involve a bioinformatician during the study design phase.

Involving a bioinformatician at the very early stages can have many benefits. In fact, an experienced bioinformatician can even help determine whether it is logical to “perform the study or not.” This may seem extreme, but believe me, it is not.

Consider a situation where you are interested in a potential drug target gene/protein and are planning to conduct an experimental study on it. Many pharmaceutical institutions have substantial internal databases that can be leveraged for this purpose. Even without any data in hand, an experienced bioinformatician can utilize public biomedical databases to assess whether the gene/protein is expressed or activated in the target tissue or cell type. Moreover, they can also investigate its expression levels in other tissues and cell types, providing early insights into potential off-target effects.

It should be noted that such a bioinformatics analysis does not, by itself, confirm or refute the decision to start a study. It is simply an input to be considered alongside other information, though it can be an important component of the decision-making process.

Involving a bioinformatician before starting a study offers additional benefits. An experienced bioinformatician can provide advice on study design, such as:

• Which NGS technology is best suited to answer the main question: Is bulk or single-cell genomics a better fit for the problem. Is multi-omic sequencing necessary?

• How many subjects/replicates and what sequencing depth are needed. Studies in cell lines, animal models and human subjects have different requirements.

• What should the background and control groups be. Background and control are used interchangeably - though they might be different in especially genetic perturbation experiments.

  
  

Having collaborated on many projects, a bioinformatics expert can also comment on additional topics, such as the quality of data generated by different service providers, and even give a rough cost estimate. Moreover, built upon the past experiences, a expert bioinformatician can provide recommendations for certain tissue- and cell type-specific experimental procedures. For example, certain epithelial cells can be highly fragile for experimentation. Or, stem cells are often very small populations in tissues and enrichment protocols may be necessary if such a population is the main focus. Certain cancer biosamples are subject to high rates of necrosis and may need special treatment. For a bioinformatician, being involved with many different biomedical projects not only provides analytical insights like these, but also a lot of biological/experimental insights and it is in your interest to benefit from all.

These are just a few examples of how consulting a bioinformatician before starting an NGS study can help. What about the cost? It is nearly nothing. Remember, you are simply gathering information from the bioinformatician (needless to say, the bioinformatician should comply with confidentiality).

Note: Image generated with ChatGPT