|Year : 2022 | Volume
| Issue : 2 | Page : 67-74
Omics approaches in cancer management: Focussing on biobanks as emerging platforms for biomarker-based precision oncology
Abhishek Mohanty1, Daniel Catchpoole2
1 Centre for Biorepository and Biobanking, Health Care Global Enterprises Limited, Bengaluru, Karnataka, India
2 The Tumour Bank Kids Research Institute, The Children's Hospital, Westmead, Australia
|Date of Submission||17-Oct-2022|
|Date of Decision||12-Nov-2022|
|Date of Acceptance||23-Nov-2022|
|Date of Web Publication||06-Feb-2023|
Dr. Abhishek Mohanty
HCG Centre for Biorepository and Biobanking, Health Care Global Enterprises Limited, HCG Towers, #8, P. Kalinga Rao Road, Sampangi Ram Nagar, Bengaluru - 560 027, Karnataka
Source of Support: None, Conflict of Interest: None
Biobanks provide a platform for innovative biomedical research of cancer etiology, progression, and prognosis and have improvised translational and personalized medicine to a great extent. They form the cornerstone, providing resources for future investigations and helping us understand the effects of genetic, environmental, and lifestyle factors on human morbidity, mortality, and health. Time 2009 published ten ideas changing the world right now with biobanks providing linkage to clinical, pathologic, and epidemiologic data of emphasizing its role in discovering and developing biomarkers in new therapeutic drugs. In this review, we highlight the emergence of biobanks as definitive platforms for biomarker discovery-based precision oncology as well as its potential to facilitate bench-to-bedside oriented and multiomics-based translational cancer research.
Keywords: Biobank, omics, precision oncology
|How to cite this article:|
Mohanty A, Catchpoole D. Omics approaches in cancer management: Focussing on biobanks as emerging platforms for biomarker-based precision oncology. J Precis Oncol 2022;2:67-74
| Introduction|| |
Multi-omic approaches coupled with recent technological advances have empowered omics to be the front runner in untangling the molecular alterations in tumors at different cellular levels and reshaping the field of personalized onco-medicine. The emergence of tumor biobanks has galvanized the field of biomarkers of drug discovery based on personalized oncology or precision oncology.
Omics are derivations of the suffix word “-ome,” which means “whole,” “all,” or “complete.” The addition of-ome to cellular molecules, such as gene, transcript, protein, and metabolite, can be referred to as genome, transcriptome, proteome, and metabolome, respectively. Omics technologies and systems biology are emerging concepts of molecular medicine. Omics refers to collective and high-throughput analyses, including genomics, transcriptomics, proteomics, metabolomics/lipidomics integrated through robust systems biology, bioinformatics and computational tools to study the mechanism, interaction and function of the cell populations' tissues and organs, and the whole organism at the molecular level. Omics-based approaches have been significantly improved recently with the addition of novel concepts such as exposomes or exposomics. This term essentially describes the study of environmental exposure to unravel the role of the environment in human diseases.
| Multi-Omics and Its Complexity|| |
The different Omics levels – Genomics, Transcriptomics, and Proteomics – vary significantly in their complexity, primarily driven by the spatial and/or temporal dynamics and chemical modifications. The flow of information in the central dogma from DNA to RNA and ultimately to protein is accompanied by an exponential increase in complexity. Recent advancements in Omics techniques have now proved to be the weapon of choice to dissect the aberrant cellular functions in multifactorial diseases such as cancer. Different Omics approaches have been developed to untangle the complexity of biological systems at different dimensions (e.g., gene, RNA, and protein levels). As we go down the pyramid, static information stored in the genomic profiling of any sample is translated to temporal dynamics and alternative splicing features at the RNA level.
Molecular fingerprinting of a cancer cell gathers the molecular data from the cancer cells in the tumor microenvironment and compares it with the normal cells, and the information is in the form of proteomic, genomic, or transcriptomic form of data or omics data. This information is fed into a data analysis platform with AI and machine learning to integrate the data to develop newer drug therapy modules and invent prognostic and diagnostic biomarkers.
| Multi-Omics and Personalised Approach to Cancer|| |
We see a massive transformation with the introduction of different omics techniques developed over the past few decades. They define different approaches, for example, whole-genome sequencing or whole-exome sequencing, driven by next sequencing, as primary techniques for describing genomics or genomics data. These high throughput data, which define genomics, have many implications in genome and exome mutation analysis, respectively. Similarly, transcriptome analysis by RNA-Seq, Epigenomics defined by methylomics, is where the DNA methylation patterns are identified by genome mapping and so forth. Thus, the two game changers in multi-omics approaches – next-generation sequencing (NGS) and liquid chromatography-mass spectrometry – have reformed the field of Omics by deciphering the human genome, transcriptome, and proteome.
With the development of these systematic analytical omics strategies, the therapeutic approach and the study of molecular mechanisms of carcinogenesis and cancer progression have moved from a hypothesis-driven targeted investigation to a data-driven untargeted investigation. The focus is completely changed from collecting information from multi-dimensional omics strategies such as genomics, transcriptomics, proteomics, metabolomics, and radiomics to the concept of integrated diagnosis, treatment, and prevention of cancer in an individual patient. This integrated approach is a prediction, preventive, and personalized medicine model. It is a promising new approach that aims to reduce cancer burden and facilitates more accurate prognosis, diagnosis, diagnostics, and effective treatment for the patients.
Omic profiling combines genomics, proteomics, and transcriptomics of early-stage disease into gene signatures that can assist in not only help in predicting which lesions will progress to a metastatic stage, but will also be of assistance in developing therapeutic options. Using these multi-omics approaches to discover novel early detection biomarkers has now been capable of stratifying the patients based on the risk–benefit ratio. These approaches of integrating genomics from different techniques have now come up with an immensely new approach to serve atypical emerging cohorts. In the current scenario, omics improvement in cancer research has led to a further understanding of the molecular mechanism which drives cancer initiation and cancer development and opened avenues for individualized patient-centric precision oncology.
There is a tandem shift in understanding how omics can bring about clinical outcomes in oncology. Omics has led to anticipating shifts in patient demographic with improved clinical outcomes. The implementation of cancer screening and early detection programs can help detect early-stage tumors, thereby increasing survival rates. In the early cancer screening programs, there is a huge opportunity, and a window for omics-based analysis and accessible malignant lesions, including all the multiple omics approaches. This shift in understanding the genomics of early disease cannot just help develop new omics-based strategies for cancer detection at early intervention but can help in developing therapeutic options.
| Prerequisites of Multi-Omics as a Tool in Cancer Clinics|| |
Data integration focuses on globally accessible information in a uniform format and is easily readable by clinicians. To make the feasibility of multi-omics a routines used tool, the need of the hour is to gather more greater data from lesser samples like single cells in a quicker time. With the decreasing cost of omics approaches in the number of diagnostic and genomics labs in the country, it is now possible to fetch the sequencing data in before than expected times and from multiple platforms. This, in turn, contributes to developing muti-omics as a molecular profiling tool to get molecular fingerprinting of a cancer cell versus tumor cell. The mandate is to collate the transcriptome and epigenome profile of tumor cells pre and posttreatment and read the molecular fingerprint during treatment and after relapse. This data are critically helpful to the clinician to monitor treatment's impact on tumor cell interaction with their microenvironment.
Integrating data have led to breakthroughs in biomarkers discovery, and such multi-omic biomarkers can tally with the treatment response of the patient, which are potential regulatory switches that mediate treatment resistance. When the patient develops resistance to drugs, these regulatory switches define why the patient is developing resistance. This information can be unearthed to develop biomarkers to help us define drug resistance indicators. For this, we need to combine multi-omics with genetics and find ways to flip switches on and off, which would lead to better patient outcomes. The tumor microenvironment needs a detailed molecular and cellular characterization which is the real challenge., This information can be translated from static genomics information to spatio-temporal protein information to predict how the patient responds to the drug treatment.
Our goal will be to make tumor cells more responsive to treatment using a multi-omics approach. Another dimension and game-changer in cancer treatment and precision oncology is Artificial Intelligence (AI) and Machine Learning methods which are now helping clinicians and researchers to stratify the existing data coming from omics approaches and present the same in a meaningful format to the physicians.
The bulk of information from genomics, transcriptomics, and proteomics put together is a vast plethora of information from a cohort of cancer patients or controls integrated and more stratified using AI algorithms wherein we identify patterns in the patient cohort to stratify them as subtypes I or II. This is important to develop at the outcome level to define the survival probability of the patient's undergoing treatment or clinical trials.
In modern times, using multiomics with artificial intelligence (AI) and machine learning has become a thorny problem. Multiomics have the potential to identify cancer-specific genes and gene sets, defining the molecular pathways involved in cancer. We can navigate patients to their best treatment options by validating these multi-omic biomarker panels using AI and machine learning.
Multi omics is becoming a platform for open discovery in cancer prevention and cure in the coming years. The long-distance vision of clinicians, researchers, and cancer biologists is to bring closer the vision of personalized cancer care to a single type of data. The patients' multi-omic footprint generated from the clinical multi-omics profiling, along with imaging information from the radiological scans, can be employed to getter a greater perception of cancer and its prognosis in the patient. We expect longitudinal multi-omics profiling of patients and their imaging and clinical data to be commonly employed to understand the disease. Integrating multi-omics data give us a complete picture of the cancer cell's molecular profile, translated into clinically relevant knowledge.
| Omics Approach in Cancer Management|| |
Precision oncology and Omics
In cancer management, integrating omics data with epidemiological data from well-defined cohorts of patients improves our ability to associate genetic alterations at the molecular level with environmental exposures. It brings out the identification of specific clinical phenotypes. All this is a means to discover this approach's potential to improve our current understanding of cancer biology and, ultimately, patient management from diagnostics to prognosis to therapeutic outcomes.
Omics have led to a complete transformation in cancer care and considering all omics approaches, there is a massive transformation in precision oncology, and the credit goes to omics. It has developed approaches to cancer treatment. They have now transitioned from conventional chemotherapy and radiotherapy options to a more personalized and targeted approach. As expected with personalized medicine, different biomarkers are to be utilized based on germline variations to somatic mutations, and this has magnanimously added to the level of personalization that can be achieved or is being achieved.
Rapid growth in understanding cancer biology and tumor cellularity has been possible due to the Hallmarks of Cancer outlined in 2000, leading to the launch of The Cancer Genome Atlas More Details (TCGA) in 2005 and subsequently opening the field of oncogenomic to identify genetic subtypes of various cancers.
Cancer is a genetic disease caused by the accumulation of mutations in DNA, leading to unrestrained cell proliferation and neoplasm formation. Oncogenomics is a relatively new subfield of genomics that applies high throughput technologies to characterize cancer-associated genes. The goal of oncogenomics over the years has been to systematically identify new oncogenes or tumor suppressor genes that may provide new insights into cancer diagnosis, predict clinical outcomes of cancers, and new targets for cancer therapies.
There is a plethora of approaches, and this multi-omic information has now come into redefining precision oncology in a very comprehensive manner, whether identifying hereditary and genetic risks n breast cancer at the screening level or diagnosing the staging at the pathological level or looking at comparison diagnosis or epidermal growth factor receptor (EGFR) specific treatment clearly outlining the prognostic pathway for cancer patients.
| Personalized Onco-Medicine Model For Cancer Diagnostics and Therapeutics|| |
Tumor biobanks are giving personalized medicine a boost in tertiary cancer centers. In cancer hospitals, the personalized cancer medicine model is now defined as how personalized medicine is being boosted by tumor biobanks in tertiary cancer centers-providing the right patient with the correct dose of the right drug at the right time.
We would need tailoring of medical treatment to a particular individual who would be defined by his/her characteristics, patterns, and patient profile. The traditional approach has always been a size fits all, and all patients with the gene diagnosis received the same treatment.
Thanks to the development of multi-omics and genetic approaches, we are now able to use this information towards a personalized medicine approach with a new treatment strategy based on the patient's unique genetic profile used to implement a strategic approach to improve individual healthcare concerning age, sex, demography, and more fingerprint and relevant costs.
| Biobanks Research Facilitating the Personalised Oncology Approach or Precision Oncology|| |
Patients are taken up for molecular and genomic testing of disease, and a thorough analysis of a patient at a molecular or genomic level helps identify the biomarkers. Thus, we can stratify the patient's response toward the drug of choice A or drug of choice B, which helps boost the personalized cancer treatment based on the discovery of biomarkers.
In other words, at the tertiary cancer hospital like HCG Cancer Hospitals, in Bangalore, India, the patients' solid tumors and body fluids, such as blood, urine, saliva, and sweat are used for molecular profiling of sample isolating genes and proteins ultimately through genomics, proteomics, epigenomics, and transcriptomics approaches. It helps identify novel single-nucleotide polymorphism (SNP) and specific mutations and ultimately transcribes to protein level or develops a biomarker that can help stratify patient's better response to drug a versus drug B.
Over the past few decades, there has been a proliferation of biobanks-both large and small that link tissue and genetic information to a host of other forms of health and personal data. Indeed, biobanking and related research methods have been characterized as an essential and potentially “revolutionizing” approach to biomedical research. In 2009, for example, a Time Magazine cover story framed biobanking as a “world changing” then, the enthusiasm has not diminished.,
Biobanks give us the handle to identify patients and get their genetic information and their clinical data. The purpose of a Biobank is to collect pathological tissue samples and information from patients suffering from a specific disease such as cancer is now used to have a more significant impact on the research discovery of biomarkers, targeted drug development, and research on the treatment of diseases or cancers.,
Tissue banks are the only houses in the surgical tissue or transplant tissue, whereas tumor banks house a tumor in frozen or formalin-fixed tissue. Various biobanks are available across the world, which is purpose-driven and single-site repositories with a specific purpose of storing the tissue samples or blood taken from leukemia patients, brain banks of Parkinson's patients, and urine and blood samples from patients from across the world.
In a cancer hospital, we need to follow something globally, and in India, we plan to develop a cohort of biorepositories across cancer institutes. The International Society for Bio Repositories (ISBER) guided the regulatory compliances to be followed to establish a tumor bank that follows the correct regulatory practices or legal, ethical, and patient ethical concerns, donor consent, and is a model system for other biorepositories to begin and establish it.,
A biorepository or a Biobank is classified as a tissue bank, or a cancer bank in a cancer hospital is composed of primarily human biospecimens. In a typical pipeline, to collect biosamples and recruit a patient or donor, consent is obtained from the patient whereby he agrees to give his biological samples (biospecimen) that could be used in a diagnostic facility to get clinical, pathological, radiological, epidemiological, and even follow-up data. This entire information is used to develop a tumor biobank facility governed by a team of experts, trained staffing process, store and manage the information in the tumor sample, and integrate it with the data stored in data management software. All this information is passed on for research, clinical trials, or commercial purpose after it goes through the Tissue Release Board (TRB). TRB essentially oversees if this process of collection of body parts (tumor cells) is being abided according to ISBER. The regulatory body in the European Commission, the British Biomedical Research Institute, defines a biobank as an organized collection of storage of Human biological samples and the associated data, which has great significance in research and personalized medicine. It is the regulatory body that helps the platform provide regulatory practices followed globally to establish a biobank, collect tissue samples, and make sure the legal and ethical part of the patient is going through a proper pipeline.
The regulatory body in the European Commission, The British Biomedical Research Institute, defines a biobank as consisting of three specific information, namely:
- It consists of biological human samples or biospecimens, which will be frozen or formalin-fixed tumor tissues
- Attached or current information that comes along with the tissue connected to the patient from whom the tissue is derived
- Patient consent and the individual data are also crucial for storing samples in a biorepository because if the same sample is utilized for research or commercial purposes, the donor must be given consent for his sample being used for these purposes and the fate of this tissue. The patient is always kept upraised on the purpose of the tissue being utilized in future.
| Biobank Versus Biorepository|| |
There is a distinct difference between a biorepository and a biobank. A biorepository stores biological materials that collect, process, store and distribute biospecimens to support future scientific investigations. Biorepositories can contain or manage specimens from animals, including humans and many other organisms.
A biobank is a type of biorepository that stores human biological samples for use and research. We start as a biobank collecting and storing samples but essentially translate into a biorepository because the samples and process are translated into the future scientific investigation, translational research, or clinical trials.
| The Fate of a Biobank|| |
The tissue bank or a biobank offers a comprehensive and versatile range of biospecimens covering the whole drug discovery and development process. A disease-oriented biobank is required to investigate diseases' molecular mechanisms, establish human disease relevance, and identify population-based cohorts for the identification of genetic risk factors. This could identify the target id for a particular marker in a population-based cohort. To identify the target id and validate it, tissue banks for investigation of the target in diseases and nonaffected organs is one way that single-cell biorepository or biobank can help markers for a particular disease like prostate cancer.
Information on tissues, body fluids, and cells is collected in clinical trials for biomarker validation companion diagnosis, but tissue banks are used to investigate target expression in large patient cohorts to support the design of clinical trials. Depending on the purpose and stage of the clinical trials, tissue bank plays a role in the clinical trials. It helps in the research, discovery, and development of the target id, which goes through validation to preclinical trials in Phase I, II, or III. Hence, biorepository is not just a storage of samples but has multiple dimensions depending on its intervention and its use.
Components of a biobank
Biobank consists of human biological material which is collected, processed, and stored. Associated confidentiality data where the patient data are anonymized and provide a unique biorepository id, and that information is a source by which we identify the patient, and this information is attached to the human biological material, which becomes a biorepository. Along with this information, biobanks also create a research database of demographical, clinical, and molecular information. Along with this, comes the regulatory information like the consent, ethical, legal, and social aspects, which is also documented for the regulatory part being governed by the ISBER practices, allowing for streamlining the biorepository's regulatory part. Patients and donors are psychologically motivated to donate samples to the biorepository as it is the patient samples with consent which ultimately is very important for the smooth functioning of the biobank.
| Old Way Versus New Way|| |
Earlier, the tissue samples from the cancer site used to go to the pathologist for staging and grading of the disease. With multi-omic approaches, the patient's tissue or blood sample is subjected to multi-omic approaches and redefined personalized medicine's fate. In a typical cancer hospital, the surgical samples collected without formalin need to be sent to the laboratory within 10 min of the excision of the tumor from the body. This is defined as the cold ischemic time because the time interval after the removal of the tumor till it reaches the storage temperature must be minimum as the biomolecules such as DNA, RNA, or genetic biomarkers are liable for degradation. Hence, the frozen sample must reach the storage temperature within 30–40 min of being excised from the body. The typical flowchart shows the transport of the samples to the laboratory after surgery without formalin, where the histopathologist confirms the tumor in the tissue along with the adjacent normal tissue sample. The cancer cells are immediately processed, barcode labeled immediately, and snap frozen at −156°C or −196°C in a cryo-storage facility or a liquid nitrogen repository transported to the site in −80°C freezers. The samples are clinically annotated with patient-associated data. Histopathology samples for formalin-fixed, paraffin-embedded blocks are transported to the laboratory in 10% neutral buffered formalin also constitutes a significant component of the biorepository. For the multi-omic approach, we require high-quality data-rich samples maintaining the cold ischemia time in addition to maintaining the integrity of the biomolecules, as it forms the most critical part in adhering to the quality control of the biological specimen.
| Liquid Biopsy– A New Approach to Biorepository|| |
Liquid biopsies encompass the practice of identifying the tumor mutations from the circulating tumor cells (CTCs) of the secreted DNA coming from the primary tumor and metastatic sites released into the circulation or blood. There is also the possibility of storing the secreting tumor cells, isolating the circulating free DNA from the cells, which can be stored as a component of the biobank. The enriched CTCs from the blood or body fluids can be stored as a component in the biobank. They can be used as reservoirs of genetic biomarkers like the circulating free DNA or RNA. The challenges of solid tumor biopsy are difficulty accessing some tumors such as pancreatic and lung cancer, mesothelia, its heterogeneity, tumor environment, repeating biopsies is a challenge, and it represents tumor at a particular time and site. The advantages of liquid biopsies are that it is low-risk, real-time, noninvasive, repeatable, cost-effective, and an effective biomarker to monitor disease progression and treatment.
| Biobanks and Radiogenomics|| |
The use of a hybrid approach that involves biobanks that integrates imaging and molecular data is an interesting patient-centric approach toward personalized onco medicine and clinical management, opening the field of radiogenomics.
Hence one of the latest goals of multi-omics biobanks is integrating imaging and genetic information to provide a more profound association between phenotype and genotype with possible imaging biomarkers. In other words, Radiogenomics emerges as a strategic approach to study genetic variation (SNP's) concerning a cancer patient's risk of developing toxicity toward radiation therapy.
One can study the genomics of tumor response to radiation therapy using a radio-genomic approach and this will involve the extracting of imaging features and its correlation with genomic data from genomic profiling like NGS, DNA sequencing, or microarrays. This blend of imaging data and DNA genomics then will provide a radio genomic footprint of a patient. It is in this area that biobanks can play a more prominent role as the tumor sample from a particular patient can be harnessed to go back to its genomic data and correlate with its imaging features to identify if the radio genomic footprint can be developed.
Biobanks as baseline platforms for developing tumor organoids:
Organoids are three-dimensional spheroids of tumor cells stacked by themselves, are homogeneously populated and can be used to identify a particular drug treatment for a single clone of cells. Biorepositories are instrumental in developing disease-specific or cancer-specific organoids, for example, triple-negative breast cancer organoids. Biobanks are used to develop a drug. Organoid cultures are a homogeneous population of single clone cells used in looking at the efficacy of a single drug in the culture model. It helps identify the drug efficacy at the invitro level, which can be used for the information that can be transcripted to identify the drug response at the personalized medicine level.
| Biobank Accomplishments in Cancer Research and Drug Discovery|| |
A significant milestone in the development of the trastuzumab antibody (Herceptin). From evaluating tumor specimens stored at National Cancer Institute's Cooperative Breast Cancer Tissue Resource, Herceptin – A game-changer in estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 + breast cancers.
Most recently, biobanks played a critical role in developing TCGA, a publicly funded project aiming to create a comprehensive “atlas” of cancer genomic profiles by cataloging significant cancer-causing genomic alterations.
Human specimens with associated clinical data facilitate the analysis of large cohorts of over 30 tumors with large-scale genome sequencing. This approach has led to the identification of several novel molecular alterations in cancer, and tumor subtypes can be classified according to distinct genomic alterations, allowing a precision medicine approach for patient care.
| A Contemporary Tumor Tissue, Body Fluids, and Patient-Derived Primary Cancer Cell Line Biorepository, a Multi-Omics Platform For Precision Oncology|| |
The idea of a world-class Tumor Banking and Primary Cancer Cell Line Biorepository [Figure 1] is to meet the needs of the pharmaceuticals, the R and D and academic/scientific community, nationally and globally, focused on cancer research under the tutelage of HCG Hospitals Bangalore. Biorepositories (or biobanks) are “libraries” where biospecimens are stored and made available to investigators for research purposes. This research provides hope to humans as well as a window to the pharmaceutical industry for the identification of new drug targets as well as the development of new diagnostic tools and prognostic models. The facility aims to offer high-quality biobanking services due to a robust and integrated infrastructure, including our histopathology, molecular laboratories, and informatics platform, as well as our highly experienced staff. The biobank will collect high-quality human biological specimens (e.g., tissue, blood, plasma, serum) and associated clinical data that are appropriately consented.
|Figure 1: A Contemporary Tumor Tissue, Body Fluids, and Patient-derived Primary Cancer Cell Line Biorepository, A Multi-Omics Platform for Precision Oncology|
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The possible scope of such services
(a) In-house tumor tissue banking and cell culture facility for developing patient-derived primary cancer cell line models for outsourcing to contract research organisations, Pharma R and D and Academic institutions locally, nationally, and internationally. (b) Selling the Dissociated tumor cells, peripheral blood mononuclear cells to R and D, Pharma companies for Preclinical screening of Drugs and Toxicity (c) Frozen tissue with paired blood–cancer patient samples for downstream applications such as genomics, proteomics, and transcriptomics.
| Conclusion|| |
The success of a multi-omics-based tumor bank is an innovation-based multiplex approach wherein, for cancer research and management, various departments in the cancer hospital need to be integrated, and the tissue repository or tumor bank orchestrates the discovery of biomarkers using the multiple dimensions in omics such as oncogenomics, deciphering cancer/individual patient-specific transcriptome, cancer proteomics, lipidomics, glycomics, metabolomics and their integration toward developing a multi-omic footprint toward patient-oriented design of novel therapeutic outcomes in onco-medicine. It is a collaborative effort between biobanks, clinicians, and researchers worldwide for precision oncology to shape into what it is today. The use of multi-omics and biobanking has contributed significantly to precision oncology and redefining next-generation oncocare and treatment options for individual patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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