Quality and security are our main priorities

There are plenty of conclusions that can interpreted of genetic data. Negen's guiding principle is to only use scientifically validated findings that are repeatable in large populations, which will ensure the usability of the genetic interpretation and reports.

Security of the stored data and user privacy has been carefully considered from the beginning of the service design.

About genetic tests

Methods

Saliva sample and isolation of genetic material

The genetic material used in Negen's gene tests, DNA, is obtained from a saliva sample, which is collected in a sampling tube provided for this purpose. The DNA contained in the saliva sample is isolated automatically. The concentration and purity of the isolated DNA is analysed and only samples that meet set quality standards are taken for post-processing. The DNA isolation and sample post-processing (i.e. genotyping) are conducted in a European laboratory specialising in the processing of genetic material.

Genotyping with microarray technology

In genotyping, the genetic information contained in the customer's DNA is determined from the samples using a DNA microarray technology. Negen uses the Illumina Infinium Global Screening Array (GSA) microarray in its genotyping. In genotyping, DNA samples pre-processed according to Illumina's guidelines are fixed to the GSA microchip and read with an Illumina iScan microarray scanner. The raw data produced by the scanner is then processed using a protocol developed for genotyping data processing, which produces quality controlled genetic data from the raw data for Negen's use.

Genetic data and imputation

Some 660,000 sites, in which variations between people are known to exist, are analysed in the DNA sample using the GSA array. Some of the analysed genome sites are known to contain an allele, or genetic variant, which can cause a predisposition to a disease or even cause a disease on its own. Genome sites causing a predisposition to a disease are also found in regions other than those found on the GSA array. We add the genetic data found in these regions to our data with bioinformatics methods, by means of imputation. The imputation of data is done in co-operation with the National Institute for Health and Welfare Biobank. Data from the genomic analysis conducted previously on thousands of Finns is used in imputation. Based on the genome sites (i.e. genetic variants) analysed on the GSA array, the genetic variant found in many of the other genome sites of the person being examined can be reliably determined. In its results report, Negen explains whether the genetic variant was genotyped directly with a GSA array or imputation was used based on other genetic variants.

Genetic analyses

Negen's gene tests are based on genetic analyses, whose methods depend on researched diseases. One genotyped genetic variant of certain diseases, such as diseases of the Finnish Disease Heritage, indicates the predisposition of the person being examined or their offspring to a disease. The results of the gene test then simply provide information on whether a person has one, two or none of the risk forms of the genetic variant in their genome. Many different genes, lifestyles, and the environment affect one's predisposition to a wide range of diseases. With respect to these multifactorial diseases, such as coronary heart disease, Negen's genetic analysis tests a large number of the genetic variants linked to the diseases in question in previous scientific studies. The tested genetic variants form a Polygenic Risk Score (PRS), which indicates the number of known genetic variants posing a risk of, for example, coronary heart disease in the genome of the person being examined. In addition to the PRS, a lifestyle survey is conducted to determine general lifestyle and environmental factors that affect the risk of contracting a disease. These include information on tobacco use, blood pressure and family history, i.e. parents suffering from a heart attack or diabetes. Information on the genetic risk of contracting a disease and lifestyle impact are combined to form a percentage that describes a person's risk of contracting a disease. Negen also tests PRSs affecting measurable traits, such as body mass index and cholesterol levels. Where these are concerned, the test produces data on the impact of a person's genome on, for example, body mass index.

The basis for Negen's risk assessments is set by analysing the impact of PRSs (i.e. genetic risk and lifestyle) on the morbidity of FINRISK participants. PRSs were calculated for 22,000 National Institute for Health and Welfare (THL) FINRISK study participants, whose lifestyle factors affecting the risk of disease and their disease history dating as far back as 20 years are known.

Data security and privacy protection

Use of the service

Negen's service is provided as a web-based application. The user is not required to download or install any separate software on their own computer. All that is required for secure use of the service is an up-to-date browser that meets current security recommendations. The service is always used over a secure connection (SSL), where all data traffic between the customer and service is heavily encrypted. Similar technology is commonly used in all online applications requiring data security, such as online banking and government transaction services. The little green padlock symbol in the address field indicates whether your connection is secure or not.

Logging in to the service

You may log in to the service with your user ID and personal password. Machine human identification is an added security measure taken to prevent automated intrusion attempts by automatically entering random login and password combinations on the login form. After five incorrect password entries, the user account will be locked out automatically for a certain period of time.

When creating a password, the system automatically checks the strength of the password and recommends using one with, for example, special characters and numbers.

Passwords are stored in the user database protected by extremely strong encryption (SHA-512) and each is assigned its own random character set, which makes breaking the encryption algorithm practically impossible.

Storing information

The Negen online service operates as a cloud service through the Amazon Web Services centre in Frankfurt, Germany. The information entered by users is saved in a database, which can only be accessed the server used for the service. No separate files containing information saved by users in the system is saved in the server. A majority of the data contained in the database is saved in a non-readable binary format. The database cannot be accessed from the Internet. The content stored on the server hard drives is encrypted.

Server-based services

In order to maintain the online service, the server must be maintained and it must perform certain tasks. In order ensure a high level of data security, only absolutely essential services are provided through the Negen server to ensure the function of the online service. Unnecessary service ports are closed, thus helping to keep the system secured.

Network security

Amazon is responsible for the data network maintenance and hardware. All cloud services are carried out within the internal network of the data centre behind state-of-the-art firewalls. Only absolutely necessary data transfer ports are opened to provide online services.

Physical data security

The data centre and Amazon Web Services are heavily guarded and under surveillance. The facility can only be accessed by those assigned specifically to work there, the assigned shift personnel and specifically invited guests. The data centre floors can only be accessed by authorised staff with two-factor authentication. The buildings are protected with intrusion detection systems and round-the-clock guard and camera surveillance. Only personnel with special permission and who are qualified to make hardware installations and repairs have access to the actual server hardware.

For additional information on data protection in the Amazon Web Service:
https://d0.awsstatic.com/whitepapers/aws-security-whitepaper.pdf

Processing and storage of samples

Customer saliva samples are collected at the Negen facility, from which they are sent to a laboratory for analysis. The samples are treated anonymously throughout the entire process, thus making it impossible for a third party to identify the origin of any sample.

Any DNA left over from the analysis is properly stored while maintaining its anonymity if the customer should need a follow-up analysis necessary in the EU area. Samples are never used for anything but Negen's analysis services without the express consent of the customer.

Quality and reliability of Negen tests

Professional skill

Negen's genetic experts are very well connected and involved in major joint research projects in their respective fields. Their knowledge of the genetics of national diseases is constantly being advanced at the forefront of international development. This expertise is also immediately transferred to Negen's gene test panels, which are updated with new information. Our years of experience in science and research allow for the critical analysis of published and produced genetic information, thus ensuring the reliability of our gene tests.

Negen's medical experts are experienced professionals from a wide range of fields in health care. Their expertise in, for example, disease prevention, treatment protocols, occupational health care and clinical genetics makes the high medical quality and usefulness of our tests possible.

Diseases and genetic variants tested

Negen's guiding principle is to only use tried and true genetic findings. This is why our product range does not include all the tests used by other operators. A high-quality genetic test can be identified by, among other things, the following principles observed by Negen:

  • The genetic variants of multifactorial diseases and traits, such as coronary heart disease, are professionally selected from the highest quality scientific research. Research charts genetic regions associated with a certain disease or trait from the entire breadth of the genome in hundreds or even thousands studied. The test is not based on just a few individual genetic variants.
  • Information on lifestyle factors plays a key role in assessing the risks of multifactorial diseases. This makes it possible to provide a highly accurate estimate of the overall risk of contracting a disease.
  • Genetic variants affecting specific diseases, such as risk variants for a predisposition to blood clotting, have been selected for the tests based on sound scientific and clinical proof. The same genetic variants are also tested in public health care.
  • The test result and conclusions based on it are explained clearly and concisely in a result report. The results also state that gene tests do not always rule out the possibility of disease.
  • Negen respects the customer's right to choose whether or not they want to know the test result. The customer chooses the diseases and traits on the result report whose results they want to review. Only then will the customer be able to see their personal results. The report also mentions the possibility of diseases and traits affecting close relatives.
  • Negen uses a certified laboratory specialising in the DNA isolation and genotyping of genetic material. The calculation methods used in producing test results are appropriate and standardised in the field of genetics.
  • On its website, Negen presents information on the methods and principles it uses in its gene tests as well as the importance of the test to health, from both a customer and physician standpoint. This allows the customer to personally weigh the importance of having a gene test based on clearly presented information prior to ordering a test.
  • Negen uses good research practices and ethics in its tests. The tests and their results are only intended for the personal use of customers 18 years and older. Tests are only conducted for diseases, against which it is possible to take preventive measures or for which there is a known treatment.

Working in co-operation with the National Institute for Health and Welfare (THL), Negen tests how genetic variants affect multifactorial diseases and traits using unique National FINRISK population data, which contains to the health history of 22,000 Finnish participants, some dating back as much as 23 years. Only when the FINRISK data has been found to have a significant connection between Negen's genetic risk score and a disease or trait, will the risk score in question be included in the Negen test panel.

The Negen test panel contains an exceptionally broad range of genetic variants. However, not all genes or genome sites related to multifactorial diseases or traits are currently known. The Negen test produces an accurate estimate based on the latest scientific knowledge concerning currently known genetic risks. As the volume of research data and key genetic markers increases, we update our analyses to ensure that our customers' reports are also brought up to date with the latest research data.

Micro array technology

The genetic variants in Negen gene tests are genotyped using the Illumina micro array technology, which is well suited to the genetic mapping of the entire genome and used extensively in different research projects. The DNA micro array can be used to capture hundreds of thousands individual oligonucleotides, thus obtaining information on a wide range of pathogenic diseases. Indeed, this is absolutely necessary where multifactorial diseases are concerned, as risk genes are scattered over different parts of the genome. Similar genome-wide data can also be obtained using the DNA sequencing method, in which a genetic structure in a certain region or the entire genome is captured as comprehensively as possible instead of analysing individual DNA sites. However, these methods are more costly when compared to micro array technology.

There is always a risk of error in all data produced with high-quality and even standardised laboratory methods. Negen has analysed the repeatability of micro array results by comparing 116,000 genetic variants and the data on six test subjects. The genotyped data for saliva samples taken from the same people at different times using two different types of micro arrays in different laboratories produced differing genetic data for 0-24 genetic variants. This results in a genotyping error rate of 0-0.02%. When the genetic risk score comprises a total of tens or thousands of genetic variants, a possible, extremely rare genotyping error for an individual genetic variant is practically inconsequential.

Quality control of methods

The genetics laboratory used by Negen is an Illumina Certified Service Provider, i.e. the manufacturer of the micro array used in the gene test has certified that the laboratory produces high-quality genome data with the method in question. There is an extensive and standardised quality control protocol for the automated processing of samples and production of genetic data at each stage of the processing. Quality control monitors, for example, the DNA concentration and purity of samples, the success of genotyping reactions for each sample, the quality of genotypes produced and their parity with previously produced data, and the repeatability of genotyping results. In cases other than multifactorial diseases and traits, the successful genotyping of genetic variants is also ensured visually one by one from the raw data produced in the laboratory.

The post-processing of genotype data by means of calculation (imputation, risk analyses) observes established methods and quality requirements. If a genetic variant planned for a gene test does not pass the prescribed variables for imputation reliability, it will not be included. Some extremely rare genetic variants cannot be imputed at all if they do not appear in the population data as the basis for imputation.