IndexThe current statusGenomics: an overviewAdvantages of genomicsDisadvantages of genomicsOther considerations: sustainability and equalityConclusionGenomics, the study of the complete genetic sequence of an organism, plays an increasingly important role in clinical medicine. This change has been made possible by the rapid development of new technologies, which can sequence a human genome in a day at a cost of less than £700. Initially, the integration of genomics into healthcare focused on the diagnosis of rare hereditary diseases and the management of cancer1. However, genomic medicine will hopefully expand into other fields, meaning all specialties will have to adapt. It is important to consider what changes will be needed, so that we can begin to develop new services and training programs. For example, will the next generation of hematologists need to learn to analyze blood smears, or would their time be better spent learning the coding languages ​​needed for genomic analysis? Indeed, will any of the current techniques used in hematology and transfusion laboratories survive the genomic revolution? Or will we come to rely entirely on genomics for all diagnostic, prognostic and therapeutic questions? Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay For genomics to replace traditional hematology techniques, the following conditions must be met. First, genomics must be superior, or at least not inferior, to currently used tests. This discussion will constitute the bulk of the essay and will include a description of current hematological tests, genomic techniques that could replace them, and their advantages and disadvantages. Second, the transition to genomic medicine should be cost-effective, environmentally sustainable, and enable equitable healthcare. The Current State of Affairs Before discussing genomics, it is important to establish the scope of tests that would be replaced. Consider a patient with chronic myelogenous leukemia (CML). The first clue to the diagnosis may be leukocytosis on the complete blood count, which microscopic analysis of the blood smear would reveal to be mostly mature granulocytes. From here, the key test would be RT-PCR or fluorescent in situ hybridization to establish the presence of the BCR-ABL oncogene which is pathognomonic for CML. Additional genetic testing helps determine prognosis, i.e., obtaining a bone marrow aspirate for karyotyping to evaluate the presence of cytogenetic changes associated with progression to the blast phase. If this patient needed a blood transfusion, serological tests would be used to determine his ABO and RhD groups. The above pathway reflects other hematologic malignancies, many of which have characteristic mutations with diagnostic and prognostic value. Similarly, genetic testing is also used in the diagnosis of inherited hematological conditions, such as sickle cell anemia.8.Genomics: an overviewFor genomics the patient journey would begin in a similar way, with the collection of blood or other fabrics. These samples must be fresh frozen to allow extraction of high-quality DNA1, which can then be amplified and sequenced using next-generation sequencing (NGS) technologies. NGS involves the simultaneous sequencing of multiple DNA fragments, the overlap between these fragments is then used to generate a complete genomic sequence. Once you get a sequence, you canbegin the extensive analysis process. For cancer patients, this would involve comparing the genomes of cancerous and healthy cells to identify mutations known or predicted to have an effect on prognosis and response to treatment. It is worth recognizing that genomics is only one branch of functional genomics. The latter field is dedicated to the study of how genes and their products function to produce aphenotype in a cell or organism. It includes many different “-omics,” transcriptomics, metabolomics, and proteomics. Since these other “-omics” require additional techniques and are less established clinically, the ability of genomics alone to replace the hematology and transfusion laboratory will be considered for the purposes of this essay. Advantages of genomics The main advantage of genomics is the enormous amount of information that can be obtained. For example, malignant cells typically exhibit large numbers of mutations, some of which determine diagnosis, prognosis, and response to treatment. This is exemplified by Ph-like acute lymphoblastic leukemia (ALL). Unlike many other subgroups of ALL, Ph-like ALL is not defined by a fundamental chromosomal rearrangement. Instead, the genome is dotted with genetic alterations in cytokine receptors and tyrosine kinases. Although this subgroup currently has an overall poor prognosis, these multiple mutations allow for the possibility of targeted therapy. Therefore, genomic evaluation of patients with possible ALL could provide rapid and accurate diagnosis of Ph-like ALL and other subgroups, personalized prognosis, and targeted therapy in a single test. As a result, genetic tests currently used in hematology laboratories, such as PCR and karyotyping, may become obsolete. Another advantage of genomics is that it can be used to evaluate molecular heterogeneity. It is well known that an individual's cancer will consist of multiple subclones, derived from a founder clone but with divergent mutations. These clonal populations can be precisely defined using genomics coupled to deep sequencing or single cell genomics. Using these techniques early in treatment can identify clones that are naturally more resistant to therapy and are therefore likely to become the predominant clone in the event of relapse. Because cancer is a dynamic disease, serial genomic sampling can also demonstrate changes in clonal populations and the development of new mutations, thus allowing changes in treatment regimens before a new clone is established. The advent of the genomic era is also likely to accelerate research. It is expected that the data generated by genomic sequencing, together with detailed clinical information, will be available to researchers. Analysis of such a database could reveal new patterns of mutations associated with disease outcome or pathogenesis. For example, the genetic basis of ALL remains undetermined in a significant minority of patients. Defining the characteristic mutations in these cases could lead to the identification of new therapeutic targets and subsequently improved survival rates. Another exciting area of ​​research is using genomic sequencing of cell-free DNA in the bloodstream to identify circulating tumor DNA (ctDNA) as a way to monitor response to treatment or detect possible malignancies. For example, in a 2012 whole genome sequencing (WGS) study of cell-free DNA from 1,002 individuals, four cases of lymphoma and one case of myelodysplastic syndrome with excess blasts were identified1. In the future, tumors maybe diagnosed, monitored and treatment decisions made using genomic analysis of ctDNA alone11, reducing the need for more invasive testing. Another area where genomics is already proving useful is the identification of disease-causing mutations in rare diseases. This application would be valuable in the management of hematological diseases believed to be the result of as yet unidentified mutations. For example, 2% of patients with bleeding disorders show no abnormalities in laboratory tests. It is thought that these patients may have defects in platelets or vessel walls12, which can be identified with genomic testing. Therefore, genomics can replace current coagulation and platelet function tests by identifying both established and novel disease-causing mutations in patients with bleeding disorders. There are further advantages to using genomics on specific genetic tests in the diagnosis of hereditary haematological disorders. For example, WGS in a patient with possible sickle cell disease could not only identify the mutation causing the disease, but could also be used to identify genetic variations that make an individual more susceptible to specific complications such as osteomyelitis. Similarly, genomes can be screened for markers that indicate drug effectiveness and susceptibility to side effects. This includes genetic variants associated with opioid sensitivity, potentially allowing for more effective analgesia in sickle cell crises or hematologic malignancies. The hope would be to produce more personalized care, resulting in more efficient allocation of resources and reduction of unnecessary suffering. Regarding transfusions, genetics is already an integral part of blood typing and is replacing traditional serological tests in some institutions. Indeed, genotyping may be superior in that it can identify antigens expressed at a level too low to be detected by a serological test or for which such a test is not available. Therefore, genetic testing allows for extensive grouping, allowing for more accurate donor-recipient matching to prevent alloimmunization. In turn, these genetic tests could be replaced by WGS, which could be used to pool all red blood cell (RBC) antigens. Disadvantages of Genomics The most significant limitation of genomic testing is that not all diseases are genetically determined. While some, such as sickle cell anemia, are determined by a single inherited genetic mutation8, others are purely environmental, for example anemia resulting from a dietary deficiency of vitamin B12. In reality, most diseases fall somewhere between these extremes, with genetic and environmental factors influencing disease development and severity. Therefore, while genomics can be used to identify individuals at increased risk for a specific condition, proving that an individual is currently affected will likely require further testing. For example, to diagnose an individual with autoimmune hemolytic anemia (AIHA), a test is needed to demonstrate the presence of antibodies directed against the patient's red blood cells. NGS techniques can be used to examine the repertoire of antibodies, however this is an incredibly complicated process. Antibody production requires B cells to rearrange and self-mutate their genome. As a result, each group of B cell clones has a unique genome that produces a unique antibody. Assessing such incredible diversity typically requires a mix of bulk and single-cell sequencing. Also in this case,The genomic sequences of B cells in peripheral blood are not a perfect representation of the antibodies present in the serum. Therefore the current AIHA test, the direct antiglobulin test, is simpler and more sensitive than genomic sequencing. The limited ability of genomics to replace antibody-based tests also has significant implications for transfusions. As discussed previously, genomics could enable more accurate matching for blood transfusions. However, given the numerous red cell antigens and limited availability of blood, it will be necessary to transfuse blood where there is a mismatch between donor and recipient for minor red cell antigens, including those with alloimmunization potential. Although only a minority of patients will develop detectable alloantibodies after transfusion, these may cause delayed or, more rarely, acute hemolytic reactions. Therefore, serological tests will continue to be necessary to identify the development of alloantibodies after transfusion. Another significant disadvantage of genomic testing is speed. WGS is significantly faster than it was twenty years ago1, however it still takes about a day to obtain a sequence and this does not include the time for sample collection, DNA extraction and analysis. As a result, WGS may not be appropriate for emergency situations. For example, blood is often needed urgently, and while O-negative blood can be safely administered, it is a precious resource with limited supply. In these cases, it seems likely that there will be an ongoing need for crossmatching, which can be done in less than an hour. Furthermore, although information gathering is an advantage of genomic testing, it is not without its drawbacks. Hematologists risk being overwhelmed by data of unclear clinical utility, a limitation demonstrated most clearly by variants of unknown significance (VUS). When genetic variations are identified in the genome, they are classified as benign or pathogenic based on evidence such as the predicted effect of the mutation or whether it has been previously observed in individuals with the disease. However, this classification is often ambiguous, giving rise to VUS variants that cannot be confirmed as benign or pathogenic. These are a significant source of frustration for both patients and doctors. Patients may worry unnecessarily about variants that are actually harmless. For clinicians, ignoring a VUS may mean ignoring a mutation that is key to pathogenesis, alternatively further investigations may waste significant time and resources determining whether a variant is benign. Likewise, the untargeted nature of genomics means that incidental or secondary findings will be commonplace. These are variants that have no impact on the primary diagnosis, but may, for example, indicate an increased risk of developing an unrelated condition. Supporters argue that these findings are useful because they could enable preventative therapy. However, this depends on the availability and effectiveness of such treatment in patients identified as at risk based on their genetic profile. Furthermore, some patients may not want to be informed of secondary results, which raises serious ethical and practical questions about how we can ensure their data remains secure and when a disclosure should be made. Other Considerations: Sustainability and Equity The transition to genomic medicine will require significant financial investments. In addition to the cost of sequencing itself, new infrastructure will be needed to transport and process clinical samples, analyze and store data, and train healthcare workers. Furthermore, in a world..