-Omics for Biologics: How Bioinformatics Is Used to Streamline Therapeutics Development
In mid-June, researchers reported that they were able to use next-generation sequencing to diagnose suspected brain infections, which are often arduous and complicated to diagnose. After taking biopsies of brain lesions, a metagenomic analysis was performed on the tissue. In a number of the patients, this lead to individualized precision treatment based on the bacteria identified.1 With all of the specialized disciplines surrounding populations of cells/organisms and the functioning parts within cells, researchers have multitudes of information at their disposal—now what?
In the process of marrying this wealth of biochemical data with computer analysis, bioinformatics was born; genomics, proteomics, viromics, metabolomics, transcriptomics, metagenomics and so on have bloomed in the presence of bioinformatics. These many disciplines, in conjunction with the analytical capabilities of bioinformatics, are the key to not only diagnosis, but to the discovery and development of biologics.
Biomarkers Are a Diagnostic Tool and Provide Clues for Therapeutic Targets
One of the most common places in which to see bioinformatics at work is oncology. Recent innovations in lab software have made it far easier for researchers to identify and track biomarkers (such as antigens) in afflicted patients. This influx of data is lending itself to phenomenal biologic developments for cancer, such as recent advances in immunotherapies for metastatic colorectal cancer (CRC), a type of cancer known for its poor long-term survival rates. Through bioinformatic analyses many biomarkers that have been identified in CRC, including the overexpression of carcinoembryonic antigen (CEA). In a recent phase 2 clinical trial, the efficacy of a chemo-vaccine combination was tested. The vaccine contained canarypox virus expressing CEA and B7-1. Researchers observed a significant increase in anti-CEA-specific T cell responses, in addition to a significant clinical response in 40% of patients.2 Modern lab software was able to play a role not only in the identification of a new therapeutic target, but also in the development of an effective vaccine.
Parkinson’s disease (PD) is difficult to accurately diagnose, especially during its early stages. Biomarkers are paramount in both the diagnosis and treatment of PD. Clinical trials of new therapeutics are often performed on those that are newly diagnosed, whom are more likely to be misdiagnosed; therefore, they are unable to effectively contribute to headway in medication development and get the care they need. Investigating the metabolome, the complete set of metabolites in a given cell, tissue or biological sample, is proving to be an effective way to search for biomarkers. Scientists are finding that significantly reduced concentrations of uric acid and increased glutathione were present in PD patients.3 Although these were only preliminary results, they do present compelling evidence that may direct the focus of PD research.
Major depression (MDD) is a devastating psychiatric disorder that affects ~16% of the population. This disorder is highly heterogeneous, presenting the necessity for better targeted therapies. Proteomics, the study of the protein complement of a cell, tissue or biological sample, is being utilized to study neurogenesis and energetic metabolism dysfunction in the olfactory bulb. By conducting 2D-gel based proteomic research, scientists were able to identify a number of up-regulated and down-regulated proteins seen in a depressed model of rats, as compared against wild-type. Through the assistance of modern lab software, researchers were able to compare their results against a database which yielded functional insights. Many canonical pathways were affected, including Wnt/Ca+ and actin cytoskeleton signaling4, few of which have previously been focused on while developing therapeutics for MDD; this is exciting news, as many MDD patients are treatment-resistant to the current regimens of MAOs, SSRIs and SNRIs. Hopefully, with the aid of further innovations in lab software, these results can be further pared down and effective therapeutic targets developed.
Meta-Analyses Provide Scientists with the Whole Picture
The gut microbiome has been all the rage in recent years. From belly dancing yogurts to costly probiotic supplements to fecal transplants, it appears to be a target that has many industries enthralled. Metagenomic analyses are able to reveal the nature of the flora in the gut and, through the aid of new laboratory software, scientists are investigating ways in which the immune system can be up regulated, how to treat diseases of the gut and how to treat other ailments throughout the body.
Dysbiosis of the gut has recently been credited with being a potential contributor to many mental illnesses and the obesity epidemic throughout North America. Since humans are born sterile, initially establishing a microbiome via the birth canal and through breast milk, scientists acknowledge that the gut microbiome is malleable. To date, there is little concrete evidence to substantiate the use of probiotics to replace missing flora or force potentially malicious bacteria out of the gut; however, profound results have been observed through fecal transplants. It will take a substantial amount of time before this therapy is accepted both federally and on a patient level, but through the aid of innovative laboratory software, there is the potential for scientists to design a substitute, a microbiome in a capsule, to perform a hard reset for a dysbiotic gut.5
Ensuring Data Is Searchable and Usable
Meta-analyses are hinged upon a slew of data that is often hard to sift through. BIOVIA Biologics provides a suite of capabilities supported by a common platform, designed to help with the discovery and optimization of biotherapeutic candidates, as well as the optimization of the overall workflow. With key capabilities like bioinformatic workflow support and predictive analytics, data mining in mountains of bioinformatic data and designing complementary therapeutics will be faster and more efficient. Please contact us today to learn more about how our software options can support the efforts of your lab.
- “Experts use next-generation genetic sequencing to diagnose suspected brain infections,” June 21, 2016, http://www.news-medical.net/news/20160621/Experts-use-next-generation-genetic-sequencing-to-diagnose-suspected-brain-infections.aspx ↩
- “Immunotherapy in colorectal cancer: What have we learned so far?” September 1, 2016, http://www.sciencedirect.com/science/article/pii/S0009898116302728 ↩
- “Metabolomic profiling to develop blood biomarkers for Parkinson’s disease,” January 25, 2008, http://brain.oxfordjournals.org/content/131/2/389 ↩
- “2D-gel based proteomics unravels Neurogenesis and Energetic Metabolism Dysfucntion of the Olfactory Bulb in CUMS rat model”, June 23, 2016, http://www.sciencedirect.com/science/article/pii/S0166432816303011 ↩
- “Application of metagenomics in the human gut microbiome,” January 21, 2015, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299332/?report=reader ↩