--------------- Complete family --------------- This mode is only available if you have a pedigree file available with your VCF or if you are using a GEMINI database (with a pedigree file in it). In the control panel you must first select the family to visualise. .. figure:: images/controls/pedigree_selection.png :figclass: align-center By default, unaffected individuals are in red and affected are in green. This color code is to defini during the pedigree analysis who must carry the variants and who must not. **The red individuals must not carry them, the green must carry them and the gray individuals are not considered (could be for individuals with unknown status).** You can change this by clicking on an individual in the pedigree tree, it will cycle through red, green and gray. .. note:: The pedigree representation as a tree is working for simple pedigrees but is not adapted for stepfamilies, multiple roots families or incestuous relations. Network tab ----------- The network tab (1 in figure below) of the control panel contains 2 parts: * the Interactions used to create the network * the pathway of gene lists that will be displayed in the network .. figure:: images/controls/network_tab.png :figclass: align-center Interactions (2) ++++++++++++++++ By default we are providing different protein-protein interactions networks. * APID [ALONSO-LOPEZ2016]_ * STRING [SZKLARCZYK2015]_ * PPI maps from Rolland et al. [ROLLAND2014]_ * a systematic co-complex PPI map [HUTTLIN2015]_ Pathway / genes (3) +++++++++++++++++++ By default we are providing several gene lists and pathways of interest for brain associated diseases such as: * Synaptic pathways from the KEGG database [KANEHISA2016]_ * Class I-III genes [YUEN2015]_ * TADA genes [SANDERS2015]_ * SFARI genes [ABRAHAMS2013]_ * FMRP targets [DARNELL2011]_ * Developmental Brain Disorder genes [GONZALEZ-MANTILLA2016]_ The user can easily create, edit, or remove list of genes. A gene list consists of a title and a list of Gene SYMBOL (one per line). Filters ------- .. figure:: images/controls/filter_tab2.png :figclass: align-center The very first option in this tab is a simple checkbox **display all genes**. When unselected, the behaviour will be to display on genes carrying variants. When selected, the network will display all the genes from the selected gene lists and pathway from the network tab. This option can be very important in several cases: * if you want to see interactions inside a pathway, if you do not check it, you will only see direct interactions between mutated genes. (no intereaction of mutated gene through a non-mutated gene) * if you want to perform a burden analysis on a pathway or a set of gene, you *must* check this box. This tab allow to filter the data on multiple criteria such as: Inheritance +++++++++++ In the complete family mode, this section is different and allow to select a genetic model for the variants to display. The 3 options are *dominant, recessive and/or compound heterozygous*. It is also possible to define if we want all the *green* individuals (affected by default) to carry the variant, or if only some of them may carry it (perfect segregation or not). In any cases, individuals in *red* should not carry those variants (incomplete penetrance is not directly considered, however it is still possible to put some individuals in *gray* so that they are just ignored). Impacts +++++++ Here it is possible to quickly filter based on the functional impact annotated by VEP. 3 quick select buttons ae available on the right side of the list: * all: select all impacts in the list * high: select impacts with a severity of HIGH for VEP, which corresponds to loss-of-function variants * med+: select impacts with a severity of HIGH or MEDIUM for VEP, which adds to the previous category variants such as missense, inframe insertion/deletions, or splice region variants Other filters +++++++++++++ The last part allows to filter on attributes from the VCF INFO fields (or GEMINI columns). Attributes types are interpreted using the VCF header. All filters condition must be fullfilled (logical AND between filters). Quality ------- .. figure:: images/controls/quality_tab.png :figclass: align-center The quality tab allows for quality filtering on the variants, based on the depth (DP), the genotyping quality (GQ) and the allelic ratio (alternate allele depth over total depth). This way it is possibly to restrict display variants to higher quality ones. The allelic ratio particularly avoids sequencing errors in lower coverage sections and mosaicism. It is possible for the user to check if the parents must fulfill the same quality filters or not. This could be important to obtain high quality variants for *de novo* mutations. But it must be noted that variant that are not passing the filters are not displayed at all. The last two options are more specific for people working on somatic mutations that were already cleaned in their pipeline. By checking the *infer GT from the AD* and setting the *Minimum AD* value, the user can set the AD threshold after which the variant is considered present. References ---------- .. [ALONSO-LOPEZ2016] Alonso-López, D., et al. `"APID interactomes: providing proteome-based interactomes with controlled quality for multiple species and derived networks." `_ Nucleic Acids Research. 44 (2016): W529-W535. .. [SZKLARCZYK2015] Szklarczyk, D., et al. `"STRING v10: protein-protein interaction networks, integrated over the tree of life." `_ Nucleic Acids Research. 43 (2015): D447-D452. .. [ROLLAND2014] Rolland, T., et al. `"A Proteome-Scale Map of the Human Interactome Network." `_ Cell. 159 (2014): 1212-1226. .. [HUTTLIN2015] Huttlin, E.L., et al. `"The BioPlex Network: A Systematic Exploration of the Human Interactome." `_ Cell. 162 (2015): 425-440. .. [KANEHISA2016] Kanehisa, M., et al. `"KEGG as a reference resource for gene and protein annotation." `_ Nucleic Acids Research. 44 (2016): D457-D462. .. [YUEN2015] Yuen, R.K.C., et al. `"Whole-genome sequencing of quartet families with autism spectrum disorder." `_ Nature Medicine. 21 (2015): 185. .. [SANDERS2015] Sanders, S.J., et al. `"Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci." `_ Neuron. 87 (2015): 1215-1233. .. [ABRAHAMS2013] Abrahams, B.S., et al. `"SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs)." `_ Molecular Autism. 4 (2013): 36. .. [DARNELL2011] Darnell, J.C., et al. `"FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism." `_ Cell. 146 (2011): 247-261. .. [GONZALEZ-MANTILLA2016] Gonzalez-Mantilla, A.J., et al. `"A Cross-Disorder Method to Identify Novel Candidate Genes for Developmental Brain Disorders." `_ JAMA Psychiatry. 73 (2016): 275-283.