Abstract the computational tools used to analyze large

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Last updated: February 22, 2019

AbstractThe healthscience field is becoming more advanced and sophisticated every year.

Withthese medical advances, it is important that medicine become suited to eachindividual in order to better diagnose and treat each person. Precisionmedicine, which takes individual variability into account, has become a largerpart of this field in recent years. Bioinformaticians have played a role inthis growth, as these scientists have developed methods for characterizingpatients through the use of genomics, proteomics, and metabolomics, and throughthe advancement of the computational tools used to analyze large sets of data.  As bioinformatics tools continue to advanceand biologic databases continue to grow, precision medicine will become agreater part of clinical practice around the world.            Bioinformatics and Precision MedicinePrecision medicine is a growing approachto preventative health and treatment of disease. This technique allows medicalprofessionals to study individuals and create a preventive and/or treatmentplan based on that study.

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This approach uses environmental and lifestylefactors along with genetic factors that are gathered thanks to the work ofbioinformatics scientists. In January 2015, Precision Medicine Initiative (PMI)was announced to extend precision medicine to all diseases and enlisted thehelp of more than a million volunteers (2016). This groups long-term goal is tocreate an electronic health record of genetic date, biological samples, andlifestyle information to help advance pharmacogenomics and lay a foundation forprecision medicine for many diseases (PMI, 2016). Precision medicinehas two main components: in the near-term a focus on cancers and long-term isto generate knowledge applicable to the whole range of health and disease(Collins & Varmus, 2015). The basis for this initiative is rooted deeply inbioinformatics. The ability to study biologic date at omics levels has led tosignificant advances in personalized medicine (Chen & Snyder, 2012). Withthe advanced study of individual omes such as the genome, epigenome, transcriptome,metabolome, and other omics, patients can be treated according to their geneticmakeup.

This changes the health field from a symptom-oriented approach to focuson preventative health and early diagnosis. In a personalized setting patientscan also be treated based on their genetic makeup. Figure 1. This shows the progression of precision medicine and the areas of focus for researchers. (Akdis & Ballas, 2016) Precision in clinicrequires five main components according to Cezmi Akdis, MD and Zuhair K.Ballas, MD.

These five components are improved disease taxonomy; includingsubgroups, full patient monitoring with digital technology, disease phenotypesand endotypes, biomarkers, and the ultimate goal of tailored individualtreatment (2016). A major aspect of personalizedmedicine to be considered is the economic impact. The global precision medicinemarket is estimated to be worth around $56 billion by the end of 2016 and isexpected to expand at an approximate compound annual growth rate (CAGR) of 14%from 2016-2024 (PMI, 2016). The market is growing due in part to the increasingapproval of drugs, the increased cost-effectiveness of DNA profiling, and therise of data-driven healthcare. As healthcare prices continue to increasepeople are looking for a personalized solution. Current State of the Field            The healthcare fields with the most promise currently are oncology andimmunology. These fields have been implementing measures of precision medicinefor years.

            Oncology isan obvious starting point in precision medicine. Given that each person’scancer is different, an individualized plan is already needed to pursue aneffective treatment plan. Each patient presents differently in clinic,prognosis, response, and tolerance to treatment. If we are better able tounderstand the biological background of cancer and how it affects the genome,we can personalize treatment to each genome.

            One issuecurrently facing researchers in cancer research is the variability seen incancer. Cancer is a highly heterogeneous disease in each patient and withinpatient populations. Because of this the ability to handle changes in theclinical trial setting is challenging (Shin, Bode, & Dong, 2017). Manyideas have not moved from bench to clinic because of the difficulty in clinicaltrials.

One promising route is the microbiota-the microorganism of a particularsite-as it has been recognized as a key player in health. The microbiotainfluences everything from disease status to drug response and resistance.Sequencing the human microbiome and discovering the interactions in individualsmay be one effective approach to increasing therapeutic outcomes (Shin, Bode,& Dong, 2017).             One notableexample of target-based therapy is the Bcr-Ablgene in chronic myeloid leukemia (CML). Using bioinformatics tools researcherswere able to develop a selective inhibitor of the Bcr-Abl.

This provided broader treatment coverage because this genefusion occurs in almost all CML patients. Survival rates improved to 90% over 5years and 88% over 8 years (Shin, Bode, & Dong, 2017). This is a majorsuccess in the path towards precision medicine but because the gene affects CMLpatients almost unilaterally it is difficult to gauge the effectiveness on abroader scale. But using the pathways and discoveries made in this arena, theresearch can be broadened to more genes and therapies.

Figure 2. A timeline of TRACERx study. The study followed 842 patients with stage l-lllA non-small cell lung cancer (NSCLC) over a three to four year period. (Jamal-Hanjani et al., 2014).

            A potential breakthrough in oncologyprecision medicine comes in the form of Lung TRACERx (TRAcking non-smallcell lung Cancer Evolution through therapy Rx). Thisapproach incorporates “multiregional and longitudinal tumor sampling andsequencing and aims to define the genomic landscape of NSCLC and to understand theimpact of tumor clonal heterogeneity upon therapeutic and survival outcome” (Jamal-Hanjaniet al., 2014). In this study samples were collected from diagnosis to relapseto gain insights into how each cancer responds to treatment, mutational processes,and the mechanisms involved in drug resistance. By taking samples from multipleregions were able to obtain a more accurate view of the genomic landscape.Also, the intratumor approach allows the researchers to gain more than a singleset of data that is set in a specific date and time.

Understanding how the subclonesof the tumor impacts clinical outcome and how these subclones interact witheach other and the host give a greater insight into the future of precisionmedicine. In conclusion, this study integrated genomic data with phenotypicresponse in order discover the heterogeneity of the cancer genome and themutational pathways involved. As with most scientific studies, it had itslimitations. Because the study relied on surplus tissue, the entire tumor wasnot sequenced. While significant coverage of the tumor was obtained a workablegenomic landscape was able to be achieved (Jamal-Hanjani et al., 2014).

Thisstudy shows the plausibility of scientific studies into precision medicine, butalso how far the field has yet to come.             Immunologyis another major starting point for those looking toward precision medicine. Thisis one of the best candidates because we currently know the main immunologicaland molecular events underlying allergic symptoms, which are the more specificand sensitive standard diagnostic tests to identify reactions, the relevantmolecules in involved in allergic reactions, and purified and standardizeddocumented products for effective and safe allergen immunotherapy (AIT) (Passalacqua & Canonica, 2015). Because AIT can modify theimmune response against the allergen it can modify the history of the diseaseitself. This is a unique factor of fighting allergies and gives it an advantagein precision medicine. There are still limitations in this field.

Biomarkersare still needed to predict the effectiveness of treatment. This biomarker identificationwould need to be researched further by bioinformaticians. A larger spread onmolecular allergy is needed in order to stick to wholly stick to precisionmedicine.

            Precisionmedicine in all aspects of healthcare requires interdisciplinary collaborationbetween experts in medical, clinical, biological, technical, translational, andbiotechnological practices (Servant et al., 2014). All of these disciplinesmust work collaboratively to build the databases and infrastructure necessaryto take on the momentous task that lies ahead of the field. Discussion            Precisionmedicine is a rapidly growing field, yet is still in its infancy. Clearly theuse of bioinformatics strategies and methods are important to this growingfield. The basis of precision medicine is understanding the human genome andother omes.

By understanding the human genome and the interaction of theprocesses within the human body the limit of precision medicine is almost nonexistent.This is a monumental task and something that bioinformatics scientists havebeen researching since the field began. The research of bioinformatics could bequite possibly the key to the breakthrough and advancement of this field.             Currentlythe field relies upon specific biological markers and instances that affect mostof the population such as with the CML gene. While this is a useful startingpoint and gives key insights into the interactions of the human body, thiscontinues to be a specific instance. By broadening the findings and techniquesused to treat diseases such as this, precision medicine can be put on a wholenew path.             Another majorshortcoming of precision medicine thus far is the public health aspect.

Inorder to fully implement this on a large scale a public health database needsto be formed with data from people of differing ethnic, environmental, andlifestyle backgrounds. With the continuing advancement of computer technologiesthis is not an impossible task in terms of computationally. The struggle in thisaspect will be the cooperation of large organizations, governments, andinternational entities.

As this is always difficult to implement, I don’t seethis kind of cooperation happening for many years, and when it does it willtake the advocacy and hard work of a major figure.             Precisionmedicine will be the healthcare of the future. With all the advancements inmedical technology and the rapid growth of the bioinformatics field, the path towardsthis type of healthcare is imminent. As bioinformatics continues to grow andadvance along with computational technology being integrated into other fieldsof science, the information to implement precision medicine will be accessiblein a fairly short period of time.             Even withall the shortcomings to this point, precision medicine has a very brightfuture.

As a young child, I was diagnosed with allergy-induced-asthma. With immunologybeing on the forefront of precision medicine since the beginning, I have beenable to see first-hand the growth and advancement of this field. To be hopefully,this field has grown immensely over a fairly short period of time. This fieldshould give hope to all that the world could soon be rid of many devastatingdisease that continually plague our society.

ConclusionEven though the scientific aspects ofprecision medicine are advancing quickly, faster than expected, the goal ofcompletely personalized medicine is far from bearing fruit. Precision medicinecannot fully be realized without public health records and databases. Populationsof varying ethnic backgrounds will have differing genetic pools and differentenvironments will have differing effects on their specific populations. Otherfactors such as access to healthcare and disease prevalence vary according togeographic location. In order to truly realize the end goal, scientificimplementation must be coupled with public health measures.

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