Innovative Genomic Analysis Solutions by Science Labs.

Clinical Exome Solution (CES)

Science Labs, in collaboration with Sophia Genetics, the Global Leader in Data-Driven Medicine, implements an even more extended, highly reliable, genomic analysis; Whole Exome Solution (WES). This new, innovative approach allows for detailed analysis of more than 19.000 human protein coding genes, according to RefSeqGenes records, covering the “expressed” portion of the human genome.

If all known Mendelian recessive genetic diseases are taken into consideration individually, their prevalence seems to be relatively low to cause any special concerns, except for some specific ones such as Thalassaemias, Cystic Fibrosis, Deafness, SMA etc. On the other hand their combined overall prevalence appears to affect a substantial proportion of our population. According to WHO (World Health Organization), the overall frequency of this type of diseases is 1% in newborns, worldwide. Moreover, hereditary diseases are causative for 20% of fetal mortality and approximately 18% of childhood morbidity, while recent publications show that more than half of future parents are mutation carriers of a (severe or less severe) recessively inherited genetic condition. Moreover, there are many cases where a patient receives a diagnosis linked to a hereditary disorder, based on clinical criteria and perhaps different types of lab and/or imaging testing. However, the genetic cause is not defined, meaning that causative genetic alterations (mutations) as well as the related gene(s) are not determined. Without this knowledge, in some cases, the identification of other high risk family members and effective family planning are not feasible.

The methodology behind Clinical Exome Solution (CES)

Science Labs is the first and, to date, the only genetic diagnostic center in Greece to implement the Clinical Exome Solution (CES) genomic analysis. Clinical Exome Solution (CES) is fully performed at our state-of-the-art lab facilities, using cutting edge technology equipment and having experienced and specialized molecular biologists and geneticists on our scientific team.

Clinical Exome Solution (CES) is developed by SOPHiA GENETICS®, the Global Leader in Data-Driven Medicine. This is an integrated approach in respect of wet lab design along with the bioinformatics analysis embedding an advanced platform, Sophia DDM® SaaS Analytics.

With the unique capture target enrichment technology and the use of the Illumina NextSeq-500 NGS sequencer, CES analyses 11 million nucleotides residing within regions which are expressed and which are related to genetic disorders, covering >4.500 genes registered in the HGMD (Human Gene Mutation Database) database, facilitating 116.355 molecular probes. Testing is performed by a specially designed analysis of all gene coding regions, their intron/exon boundaries as well as other known regulatory elements residing outside genes which are known to contribute to an abnormal phenotype. The method implemented detects nucleotide substitutions, small deletions/duplications and some balanced rearrangements. Therefore, performing one single test there is access to genetic information, which would be extremely difficult to gain by single gene testing conducted in a single lab.

Clinical Exome Solution (CES) analysis method allows for exceptional analytical performance (sensitivity >99%, specificity >99%, reproducibility >99%), with a median coverage greater than 50x in over 96% of targeted regions, presenting unsurpassed uniformity in coverage (>98%).

What has changed with new technologies?

Until recently, in order to investigate genes related to genetic disorders, step-by-step single gene analysis or, best case, small panel gene analysis were performed. Therefore, testing was time consuming, laborious and with a high overall cost burdening the patients. Nowadays, platforms exploiting new technologies, such as Next Generation Sequencing (NGS), allow for massive parallel sequencing of a great number of genes in the same assay, overcoming the aforementioned limitations. Thus, the cost per gene is dramatically reduced and, by obtaining more rapidly, reliable results, referring doctors and their patients gain valuable information in the aim of effective healthcare management for patients and their families.

Why is Clinical Exome Solution (CES) superior compared to other approaches?

Clinical Exome Solution (CES), which is implemented exclusively by Science Labs, exploits new technologies throughout all steps, allowing for simultaneous analysis of more than 4.500 genes. Therefore, reliable genetic investigation is obtained, at a low cost per gene and at a much shorter turn-around-time. Clinical Exome Solution (CES), performed exclusively at Science Labs, is superior to other comparable methodologies, since apart from its high performance potential, it presents higher levels of uniformity in regions of clinical interest, even at the most demanding ones, such as promoter regions and first exons, which have a high GC content.

Combining all its characteristics, it’s the method with the less false negative results.

Compared to broader approaches such as WES (Whole Exome Sequencing) and WGS (Whole Genome Sequencing) Clinical Exome Solution (CES) is more targeted to regions with proven clinical significance. As a result, deeper coverage is achieved, making causative mutation detection easier, more effective and precise. In any case, to date there are no systematic studies supporting whole genome analysis in healthy individuals while, on the contrary, there are recent publication recommending not to proceed with such broad testing for numerous reasons.

Bioinformatics data analysis, by using the Sophia DDM® SaaS Analytics platform, provides the option to store analysis data for up to 10 years, in an easily accessible way and on secure mode concerning privacy issues. Thus, while a an initial subset of genes of interest may be analyzed directly after testing, there is an option for retrospective analysis of another subset of genes in the future depending on current needs. As an example, by undergoing testing only once, an investigation of a neurological condition may be performed at first and, without repeating the test, predisposition to hereditary cancer may be evaluated subsequently.

Who is a candidate for testing with Clinical Exome Solution (CES)?

For an extended carrier screening, in the context of family planning, Clinical Exome Solution (CES), performed at Science Labs is the method of choice. By being tested only once, potentially, up to 4.500 genes which are known to contribute to an abnormal phenotype related to severe or less severe genetic disorders. Mutation carriers of many genetic diseases, especially those inherited in a mendelian recessive manner, present no profound symptoms. Thus, healthy carriers have a high risk of giving birth to affected children.

For an extended carrier screening, in the context of family planning, Clinical Exome Solution (CES), performed at Science Labs is a method of choice, especially for couples entering an IVF program. Taking into consideration the multilevel complexity of these procedures, the knowledge of mutation carrier status and the probability to co-inherit mutations leading to a recessive genetic disorder may be proven valuable. Thus, prenatal diagnosis or preimplantation genetic diagnosis and selection could be timely scheduled or future parents may prepare for the future. Additionally, CES may be performed on sperm/egg donor candidates in order to estimate the genetic burden of the donors prior to IVF.

For the investigation of genetic causes of unexplained infertility, Clinical Exome Solution (CES), performed at Science Labs, may broaden the spectrum of testing beyond standard testing approaches, so that valuable information is gained to choose the IVF program most fit for each couple.

In pediatric or adult cases, where the genetic grounds of a clinically suspected/diagnosed disorder needs to be revealed for the most effective healthcare planning and management, Clinical Exome Solution (CES), performed at Science Labs, may prove to be a valuable asset for the pediatrician’s, cardiologist’s, neurologist’s, ophthalmologist’s and various more specialty’s clinical practice.

Clinical Exome Solution (CES) genomic analysis method, performed at Science labs, is a comprehensive approach and the knowledge gained may contribute as a determining component to the genetic counselor’s, clinical geneticist’s and other specialty’s best practice.

Brochure

The disease spectrum investigated by the Clinical Exome Solution (CES)

Autism spectrum disorders

ΚCardiomyopathies

Ciliopathies

Congenital disorders of glycosylation

Congenital myasthenic syndromes

Epilepsy and seizure disorders

Eye disorders

Glycogen storage disorders

Hearing loss

Hereditary cancer syndrome

Hereditary periodic fever syndromes

Inflammatory bowel disease

Lysosomal storage disorders

Maturity onset diabetes of the young

Multiple epiphyseal dysplasia

Neuromuscular disorders

Noonan syndrome and related disorders

Peroxisome biogenesis disorders

Unexplained infertility

Zellweger syndrome spectrum

Short stature panel

Skeletal dysplasia

X-linked intellectual disability

Unlocking the Power of Clinical Exome Sequencing For Diagnostics

Clinical Exome Panel

Το σύνολο των γονιδίων που ελέγχεται με το Clinical Exome

GENES

Frequently Asked Questions

1What are the benefits of ordering Science Labs’ Clinical Exome Solution for my patients?

There are many benefits linked to Clinical Exome Solution (CES) for you and your patients. Overall, a clinical exome sequence for a patient will help you better predict their risk for a disease, to verify or exclude a clinical suspicion, while understanding the underlying genetic etiology of existing conditions. Having a patient's clinical exome sequenced also means that >4.500 gene code is available for re-examination at any point without having to repeat the lab test. Feel free to contact us for more information.

2Can patients order tests directly from Science Labs without a physician?
No, patients cannot order without a physician's approval. We do encourage everyone who is submitting a sample for testing to provide us with his or her own physician's information, as this is extremely important for follow-up after testing. We want to ensure that everyone who has Clinical Exome Solution testing has appropriate counseling, medical care, and treatment, if indicated, following receipt of his or her test results. Informed consent by the patient is crucial prior to testing, as well.

3How often should a clinical exome be sequenced?
Having a CES completed once, since it does not change means that as more scientific discoveries are made and as their clinical relevance becomes known, more useful information can be made available to you and to your patients. For example, we can initially evaluate cardiac defect related genes, and as knowledge grows along with ongoing needs, a patient's records can be updated with additional interpretation of the already stored clinical exome sequence. Data are safely stored for 10 years. Additional interpretation of health-related matters will require physician participation and may require genetic counseling.

4What is the clinical value of clinical exome solution (CES)?
Through Science Labs’ Clinical Exome Solution, your patients may learn about a variety of health and lifestyle conditions that may affect how you monitor their health, tailor annual exams, and recommend monitoring frequency. Understanding an individual patient’s particular risk allows for proactive, precision medicine, rather than treating all patients with the same, ‘one size fits all’ protocol. For example, when an individual who is identified as a BRCA1/2 mutation carrier during CES and who otherwise would not be at high risk because of ethnicity or family history alone, a different observation and monitoring plan with a potentially much better outcome can be initiated. But it’s not all about disease. Knowing lifestyle traits such as athletic, metabolic and nutritional genetic preferences may help you guide a patient towards lifestyle changes that could improve their health and quality of life. Two simple examples are their approach to exercise (e.g. elect long distance versus interval training) and the foods they eat (e.g. manage iron intake with an elevated risk of Hemochromatosis.)

5How would your test help my practice?
Genetic information can be used on an on-going basis to manage a patient's disease risks proactively rather than reactively. Sequencing the clinically significant exome may also offer significant cost savings overall when compared to ordering other inferior genetic screening tests.

6Is genetic counseling offered with your service?
Depending on your circumstances, genetic counseling pre and post test can be offered either by your own physician/institute or by a specialized collaborator of ours. You may also request re-examination of the genome at a later time for further interpretation and counseling. These additional services are available by request to you for an additional fee.

7Do’s and Don’ts of Clinical Exome Solution
If you are interested in extended carrier screening in the context of reproduction choice planning, couples undergoing IVF, egg/sperm donors and unexplained infertility, Clinical Exome Solution is a method of choice. It may prove to be valuable for pediatric or adult cases with a genetic disease/disorder of unknown genetic etiology in order to effectively implement healthcare planning. Clinical Exome Solution may be a useful source of information for the pediatrician’s, cardiologist’s, neurologist’s, ophthalmologist’s, endocrinologist’s and other specialties practice. With multi gene Massive Parallel Sequencing, implemented by CES, cost per gene is significantly reduced and by getting faster, reliable results physicians and their patients gain valuable information for better to-the-point management of their health issues affecting both themselves and their families.

8What types of variants are reported with Clinical Exome Solution?
Science Labs’ Clinical Exome Solution report records only patient’s phenotype related pathogenic or likely pathogenic findings. Classification is based on HMGD, ClinVar, Exac and HPO (Human Phenotype Ontogeny) databases and according to the guidelines of ACMG. Variants which are of unknown clinical significance, do not lead to amino acid substitution or are classified as benign or likely-benign are not reported unless there is evidence or are predicted to contribute to the phenotype and the referring physician requests otherwise.

9Who can benefit from Clinical Exome Solution (CES) analysis?
Αν ενδιαφέρεστε για εκτενή έλεγχο φορέων στα πλαίσια του οικογενειακού προγραμματισμού, για ζευγάρια που πρόκειται να ενταχθούν σε πρόγραμμα υποβοηθούμενης αναπαραγωγής, υποψήφιους δότες γαμετών και τη διερεύνηση των γενετικών αιτίων της ανεξήγητης υπογονιμότητας, η CES είναι μέθοδος επιλογής. Επίσης, είναι ιδιαίτερα χρήσιμη σε παιδιατρικά περιστατικά ή περιστατικά ενηλίκων, όπου η κλινική διάγνωση της νόσου ή διαταραχής χρήζει εργαστηριακής τεκμηρίωσης, ώστε να σχεδιαστεί αποτελεσματικότερη αντιμετώπιση. Το CES είναι χρήσιμο για την πρακτική του παιδιάτρου, αναπτυξιολόγου, καρδιολόγου, νευρολόγου, οφθαλμιάτρου, ενδοκρινολόγου και άλλων ιατρικών ειδικοτήτων. Με τη μαζική παράλληλη αλληλούχηση πολλών γονιδίων, στην ίδια εξέταση, το κόστος ανά γονίδιο μειώνεται σημαντικά, και παίρνοντας ταχύτερα αξιόπιστα αποτελέσματα, οι θεράποντες ιατροί και οι εξεταζόμενοι αποκτούν πολύτιμη πληροφορία για την αποτελεσματικότερη διαχείριση της υγείας των άμεσα ενδιαφερομένων και των συγγενών τους.

10What is an Informed Consent and why do I have to sign one in order to get Clinical Exome Solution testing?
Your physician’s Reason for Referral form should be coupled with a signed Informed Consent. Information in this document includes, but is not limited to, testing abilities and restrictions as well as the gene subgroup to be analyzed in the specific test order, based on your personal or family history and/or your phenotype. Its main purpose is to ensure that you fully understand what you are tested for, what you may expect out of these test results and it is important for personal genetic data security issues. It is strongly recommended to sign this form after being thoroughly informed and following genetic counseling by your doctor or a specialist.

GENOMIC ANALYSIS CONSENT FORM

GENOMIC ANALYSIS REQUISITION FORM

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