Revvity blog

Faster insights and better science in the search for desperately needed new therapies

August 3, 2018
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In a previous post we noted the increasing importance of biologics as therapeutic agents, with 37% of the drugs approved by the FDA in 2017 being biologic entities. A recent article in Chemical & Engineering News (June 4, 2018, pp 28-33) focused on activities in immuno-oncology, where biologic checkpoint inhibitors are being tested in combination with other immunotherapies: there are currently ca. 250 small molecule- and antibody-based immunotherapies in clinical studies, and > 1100 clinical trials in 2017 combined a checkpoint inhibitor with another treatment.

With this increasingly urgent drive to discover and develop novel bio therapeutics in areas such as oncology, it is crucial that researchers are equipped with the best possible tools to capture, manage and exploit all the available data, and we commented that “In the area SAR and bioSAR, underlying chemical structural and bio-sequence intelligence are key requirements for meaningful exploration and analysis, and these are often only available in separate and distinct applications with different user interfaces, when ideally they should be accessible through a unified chemistry/bio-sequence search and display application, supported by a full range of substructure and sequence analysis and display tools.”

In this post we drill into these requirements in more detail and discuss how an ideal bioSAR tool should support faster insights and better science in the search for desperately needed new therapies.

As we noted previously, researchers are struggling with a data deluge, and need effective tools to locate, extract, sift and filter relevant data for further detailed visualization and analysis. With biologics, these applications will need to understand and manage bio-sequences, and an immediate requirement will be to allow sequence searching, using a standard tool such as BLAST to search across internal and external sequence collections, to collect and import the appropriate hits in a standard format, and to link them to other pertinent properties (bioactivity, toxicity, physicochemical, DMPK, production, etc.)

With a tractable data set on hand, researchers will want to explore sequences to try to discern particular motifs or sequence differences that are correlated with bioactivity or desired physicochemical or DMPK profiles, and thus potentially amenable to further manipulation and enhancement.

The sequences must be aligned, for example by CLUSTAL Omega, and visualizations should present sequences so that sequence differences are immediately highlighted, and monomer substitutions can be explored for potential links to bio-therapeutic activity. LOGO plots to investigate the distribution of monomers in a set of sequences, and annotations to highlight and share areas of interest will also help researchers to get to insights more quickly.

If scientists want a deeper dive into the underlying structure of the sequence or a region, immediate access to a detailed and interactive 3D rendering of the biomolecule’s structure can provide a different lens through which to understand how different monomers substitutions may impact protein folding or active site binding and thus activity.

There may also be cases where required specialized analysis or visualization capabilities are only available in a separate in-house developed, third party, or open-source application, and the provision of an extensible Web Services framework will enable these to be quickly linked in to an enhanced analysis pipeline that can then be shared with colleagues and collaborators.

A bioSAR system providing the capabilities discussed above, equipped with an intuitive and unified user interface catering for novice and power users alike will enable them to derive faster incisive insights and make better informed scientific decisions in the search for novel bio therapeutic agents targeting some of the world’s most pressing unmet clinical needs.

Accelerate analysis of sequence differences relative to a reference sequence.



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