Genetalk is a web-based platform for the exchange of information about disease relevant DNA sequence variants. Since next-generation sequencing like exomes or whole genome sequencing has become a useful tool in personalized medicine. There is a requirement of time-consuming effort for the assessment and interpretation of detected personal variants in the clinical context. This is countered by using genetalk a web-based platform. This platform aids a clinical geneticist in searching information about specific sequence variants. It also helps user interconnect each other with expertise for the same sequence variant.

Current Scenario

In case of a novel potential mutation in rare diseases are mostly based on variation data from a small population scale. But most mutations are medically irrelevant like in case of monogenic mutation. Many bioinformatics tools are used for annotation of prediction of the expected pathogenicity of the variant. But these classifiers have high error rates. These errors may be false-positive and also false-negative. Thus these tools may be considered as prioritization tools, not as a final tool in detection. For finalizing the assessment of the pathogenicity of these mutants human expertize is always needed and human analysis should be considered as the ultimate assessment tool.


In cases of the genetic disease whose causative gene is unknown, there are few possibilities of the origin. It may be due to the association with a new disease gene. This association can be visualized by a functional assessment of the detected variants or by statistical evidence. Speaking of functional assessment the following requisites are needed: a suitable test assay, or a genetically modified organism. In case of statistical assessment the requirement of a large number of patients, with the same disease and same mutation is needed.  This statistical assessment is really hard when the exome analysis of a rare disease is analyzed. It is also limited by the expertise of a clinical geneticist in functional assessment.  Hence the requirement of the finding of another geneticist with mutations in the same gene or scientists that are performing basic research on this gene. There are a lot of knowledge-based management platform in different platforms of scientific fields. For example, there are knowledge bases for disease, gene, and protein-centered information. Genetalk aims at providing such a web-based platform that enables to improve expert annotations on human genetic variants in a community approach.

According to the web-based tool on the internet. the following steps are to be followed to use Gene talk. It is an online tool for the geneticist. The following procedure is followed for a new user.

How to use Genetalk

A five-step process is required to assess your gene variant. All the data of the gene is used as Variant Caller Format (VCF) format.

  1. The first step is to upload your sequence variants. It can be from single or multiple samples. As mentioned earlier the file should be in a VCF format. When uploading makes sure to have a reference hg19 or GRCh37. Both the reference are similar and referred to the human genome clones sequenced during human genome project. After uploading the files are automatically enlisted in the file manager. these files can be viewed by clicking the file name and can be shared with others.
  2. The next step is the analysis and editing the pedigree and phenotype of the individual variants in the VCF file. Specification of phenotypic features is done according to the Human Phenotype Ontology. This information helps in the efficient filtering of the variants.
  3. The next step is the filtering the VCF file. They are a variety of filters available in the genetalk tool. One can choose the filters and number of them based on the application or need. The number of filters used help in reducing the number of variants in the VCF file.

Types of filter

Functional Filter: This filter reduces the number of variants which may have an effect on the protein level.

Linkage Filter and Gene Panel Filter: The main factor of this filter is a particular set of genes or a particular linkage interval.

Frequency Filter: it is a statistical filter that reduces the variants based on the background population. If genotype variants occur than the more than the adjustable cutoff it is removed.

Inheritance Filter: When a variant is attached to a certain mode of inheritance it is filtered.

  1. View Sequence Variants

After the filtration is done the VCF file have a lesser number of sequence variants. Then we start on an annotation to find the annotation of the variants.

Annotation can be defined as the user-generated content specific genomic position about a genetic disorder or others. When an annotation is found it includes more details about it. It contains links to scientific articles, subjects medical relevance, scientific evidence, and also comments from other users. From the annotation, a user can start a discussion.

5 … Find Annotations, Experts, and Patients: As explained earlier the annotation column indicates a variety of files linked with a particular annotation.  The annotations column indicates if for the position exists at least one annotation, an expert, or another patient. Clicking the annotation column opens the list of annotations, experts, and patients.

How to Find Annotations

Genetalk has numerous ways to find an annotation.

  1. Open a VCF file in the file manager.There arises a list of icons which include an expert icon, a patient icon, or a rating icon. The rating icon shows that there are annotations for a variant. One can click on the rating icons, this opens a list of annotations for this variant.
  2. Search for a gene to find all annotations for a gene.
  3. Search by genomic position.

How to Add Annotations

To add annotations just click the Annotate button in the VCF viewer to add an annotation. There are options for a used one can choose, whether an annotation is visible just for the users, for a selected group of GeneTalk users, or publicly visible.

Ratings for Annotations

The rating system provides the significance of the annotation for Medical Relevance and Scientific Evidence range. It varies from one star, which indicates an irrelevant/artifact and very low disease-causing possibility, to five stars which mention the annotations high capability for disease-causing. New annotations must have voted for both medical relevance and scientific evidence. The ratings as always are fixed by the majority of the user’s votes. It is automatically updated when a new high is found.

Gene talks Knowledgebase

The knowledge base of GeneTalk is a combination of annotations from publicly available databases. For example, If an annotations “disease-causing” from ClinVar is initialized in a GeneTalk’s, Immediately medical relevance ranking for the annotation starts with 5 stars.If a Sequence variant initiated in Genetalk is classified as common artifacts in the 1000 genomes project, it is given a rating of one star medically irrelevant. But, When a variant of unknown clinical significance, VUCS, is initiated the wisdom of the crowd is used for rating. Genital encourages the users to contribute their own ranking so that the status of each VUCS.

Filtering Variants Using Annotation Votes

The filtering process used in the GeneTalk‘s annotation filter can be fixed at any level of medical relevance and scientific evidence. For example, To remove all medically irrelevant variants to be removed one can set a filter is two stars in medical relevance. This removes all sequencing artifacts and irrelevant variants. The filter settings are at the choice of the user. The user should e reasonable to start with a five-star rating for medical relevance and at least a two-star rating for scientific evidence.When an annotation step is ignored one can lose a lot of useful information about the variants. This setting can be used to check if there are variants in a dataset with known mutations. If a patient cannot be diagnosed using this setting, it is a more elaborated research question and other filtering parameters have to be chosen.

There are many heterogenic disorders which can be caused by pathogenic mutations. These pathogenic mutations can occur in tens or even hundreds of genes.Sequence data of these genes are created by using next-generation sequencing methods sequencing can be done in all such genes or even the whole exome or genome. GeneTalk‘s Gene Panels help you analyzing the sequence variants in certain regions of interest efficiently. Genetalk has a filter of such kind that can be used to filter all genes related to a molecular pathway or genes associated with a certain phenotype. This filter is termed as a gene panel. Gene panel can also be used as means of filtering the expertise. Also, it helps in declaring the expertise of a particular user.

Gene Panels: Filtering and Expertise

One can create their own Genepanel in Gentealk. They can edit the number of people and edit and also their gene panel with the other users. Also one can subscribe to public gene panels. A user can use these Gene panels for filtering and to stay up-to-date: This can be done simply by checking the box in the list of public gene panels and clicking on Subscribe. The gene panel will now be listed in My Gene panels. When a gene panel is modified or commentated, all subscribers to the panel will be notified.

A new Genepanel can be created using the following steps:

First, click New Panel. A dialog box will appear. This is helpful for generating a gene panel. Paste a list of genes or genomic regions in the Genes text box. Give a short description for your panel. You can label for gene panel. If you want other users to allow to use your gene panel for filtering  Check Publish for filtering.

Filtering with Gene Panels

In case of filtering files for variants in a set of genes that are associated with a particular disorder use the Gene Panel tab in the filter menu. Select one of your – own or subscribed – gene panels. You can also enter one or more genes in the text box. Set other filter parameters to your need, and click the Filter button at the bottom of the page to start the filter process.

Your Field of Expertise

If you want other users to contact you, for example, to discuss variants in genes you are interested in, define a set of genes as your expertise. You can state an expert level for every gene panel you created or subscribed (My GeneTalk à Gene Panels à edit icon ). You will then be visible to other users, for example, in the annotation list for a variant.

If you do not already have an expert gene panel, open your profile (My Genetalk à My Profile or click on your username in the title bar) and enter a list of genes and a short description in the Expertise tab.

Finding and contacting experts

If you click on a gene name anywhere in GeneTalk (or search for it using Search GeneTalk à Genes) you will get information about the gene itself, annotations to variants in this gene, and a list of experts. You can contact expert users by clicking on the envelope button next to the username or – vice versa – others can contact you if you are listed as an expert in this gene.

GeneTalk offers an efficient filter for compound heterozygous sequence variants. Open the Filter menu and select a VCF file that is listed under Collections (i.e, the file contains at least a set of three individuals and is supplied with pedigree information). Now, you will find the compound heterozygous filter option in the Inheritance Filter tab.

Recessive Compound Heterozygous Filter Rules

To be transmitted in a compound heterozygous mode from parents to the patient, a variant must meet the following conditions:

  1. The variant is heterozygous in all affected individuals.
  2. The variant is not homozygous in any of the unaffected individuals.
  3. The variant is heterozygous in exactly one of the parents if it is heterozygous in an affected child.
  4. The variant is not heterozygous in both parents.
  5. The variant is present in at least one parent.
  6. There is at least a second heterozygous variant in the same gene in each of the affected individuals.
  7. There is at least one variant transmitted from the paternal side and one transmitted from the maternal side


In most cases of recessive genetic disorders, a malfunctioning gene is present in all copies. For autosomal recessive genes all maternal and paternal gene harbors a pathogenic mutation. Over time there a lot of cases of different pathogenic mutations have arisen from recessive genes and the occurrence of a mutation is a random process. The chance of two different mutant alleles of the disease-causing gene is indirectly proportional to the lower the kinship of the parents. For a recessive disease, the likelihood of occurring is possible if the parents are nonconsanguineous, compound heterozygosity. The challenge in filtering sequence variants for compound heterozygotes is how the different copies affect one or different genes.  This kind of information is not available from a single DNA sequence when the read length is smaller than the distance between the variants. For this scenario, the exome sequence of more than one family members is available Mendelian inheritance can be used to exclude certain variants.


Here in this example, we demonstrate the use of genetalk in a case of schizophrenia. For this purpose, an interview study is carried out involving 19 participants. The interview was about how and for what purposes participants indulged themselves ‘gene talk.

In the last two decades, psychiatric genetics has grown in prominence. As the field has grown, Models are proposed by psychiatric genetics. These models intrigue social scientists and clinicians how they affect diagnosed individuals and family members conceptualize the etiology of mental illness. These models also interest people on the emphasis biogenetic factors might reduce the stigma of mental illness and well as the blame and guilt frequently experienced both by those who receive psychiatric diagnoses and those related to them. The implications of these biogenetic factors are the growing indications do not reduce at the population level. For a different group of peoples, the implications differ variedly. These models in different studies have shown that the biogenetic factors reduce or might reduce stigma and blame by shifting the culpability from an individual to hereditary.