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Add new case page > Family tree screen > Create family tree panel
Build a pedigree via the visual tool.
It is ideal that a proband selected for case analysis is affected and has disease phenotype(s).
You can add a Father, a Mother, a Sibling, or a Child to any family member, starting with the Proband. To do this, choose their icon, then click on the Add family member button in the bottom right corner of the pedigree builder to select a family member.
More information about the pedigree symbols can be found here.
To delete a family member, choose their icon, then click on the Delete Subject button in the top right corner of the Add patient information panel.
Note: There is no technical limit on the size or number of generations for a family tree.
When creating a new case, the first step is to select the sample input type. This determines how your data will be processed and which quality metrics will be available later in the analysis.
You can choose from the following supported formats: , , and .
Use this option if you want the platform to perform secondary analysis and variant calling.
.fastq.gz
.fq.gz
.bam
.cram. Make sure you understand the current limitation for using CRAM files by expanding the section below.
Context
Emedgene uses a specific genome reference assembly file (for example, hg38-alt_masked.cnv.graph.hla.rna-10-r4.0-1.tar.gz) for each DRAGEN version + genome reference (GRCh38 or GRCh37) combination. Both DRAGEN version and genome reference are configured per organization in Workbench & Pipeline settings.
Key requirement
When using CRAM files as input (instead of BAM), the same genome reference assembly file must be used during:
The mapping/alignment stage (which produces the CRAM file)
The variant calling stage (Emedgene secondary pipeline)
A mismatch in reference genome assembly files prevents the system from decompressing the CRAM file, leading to case analysis failure.
Best practices
Confirm reference compatibility with your organization settings before launching a run
If you receive CRAM files from an external lab, verify the specific reference genome file used to generate them
If the reference is unknown or incompatible, convert CRAM → BAM and upload the BAM file instead
Use when working with a joint VCF file containing multiple samples.
Accepted file types:
.pvcf
.vcf
.pvcf.gz
.vcf.gz
Make sure the proband sample is listed first to ensure correct downstream calculations.
Use for cases where variants have already been called externally, or for cytogenetic array inputs.
Accepted file types:
.vcf
.vcf.gz
.targeted.json
.gt_sample_summary.json (v37.0+, DRAGEN Array v1.2+)
.annotated_cyto.json (v100.39.0+, DRAGEN Array v1.3+)
Array results can be visualized in Genome View and the IGV tab, and sample-level quality metrics are available under the Lab tab.
Tips:
Choose the input type carefully — it cannot be changed after the case is created.
Keep file paths simple (avoid spaces, parentheses, or very long names >255 characters). This helps prevent errors during upload.
Warning:
If files are incomplete or corrupted, the case may still be created but will fail during processing. Double-check your files before uploading.
For large files (BAM/CRAM/FASTQ), browser upload is not recommended. Use , , or cloud-to-cloud transfer instead to avoid incomplete or truncated uploads.
Users can utilize a custom region of interest (ROI) BED file to limit analysis results to variants within the designated regions. A ROI BED determines which genomic regions will be included in the variant analysis.
BED files that define custom kits can be added in the Organization settings under Kit management.
If no custom ROI BED is selected, the system uses the default ROI BED file based on the case type.
You can select any region of interest, regardless of the case type.
When selecting a Custom BED as you region of interest, you must select a specific BED file that is already configured in your organization.
Add new case page > Case info screen > Select genes list
You can limit analysis to a gene list in the platform while creating a case. Choose between:
No limitation of the analysis.
Select one of the previously added gene lists from a dropdown list.
Generate a new virtual panel: add a List title and then add all the gene symbols one by one () or in a batch ().
A new gene list can be comprised from a combination of configured gene lists and/or individual genes.
A gene list can by configured to hold up to 10,000 genes.
A new gene list can be created by combining configured gene lists and/or individual genes. Each gene list can be configured to contain up to 10,000 genes.
Note: Please use the up-to-date gene symbols approved by the Hugo Gene Nomenclature Committee. When adding gene symbols in a Batch mode, those genes that do not comply with HGNC standards will be automatically excluded from the gene list. These genes will appear for 3 seconds in a black error box at the bottom of the screen.
For each gene please follow the steps described below: Enter a gene symbol in the search box in the right panel (Candidate Genes) and select a matching symbol from a dropdown menu.
After selecting batch mode, paste a list of comma-separated gene symbols in the search box in the right panel (Candidate Genes).
You can choose between two different modes of a gene list feature:
Selected by default.
AI Shortlist is limited to the selected gene panel, no variants in other genes are considered in the results. If this in silico panel is used for analysis of exome or genome data, the gene restriction may be lifted during manual analysis to "open-up" the entire exome or genome for analysis.
Analysis is performed for variants in all the genes. Variants in the targeted genes get upgraded scores during prioritization by the AI Shortlist algorithm.
You have the flexibility to manage Case labels at any time: create, add, or remove them directly in the Cases table.
Adding labels to a case provides the ability to quickly mark cases for specific use cases and an easy filtering of cases sub set in the cases page.
You can implement different combinations of Presets to be used for different case types (i.e. Presets for exome may be different from Presets for genome) as defined by your SOPs to further streamline case review.
The combination of Presets is referred to as a Preset group.
Preset group selection is available in the Case info screen of the Add new case flow while creating or a case.
To manage filter Preset groups, navigate to > > :
From here, you can create ( /, , and Preset groups as needed.
Here, you can set a Preset group as default, so it will be used unless another Preset group is selected during .
While adding a new case, you will build a pedigree and annotate each of the samples with data required for analysis (Add new case page > Family tree screen).
After the case has been created, the family tree is available in the Case details panel (righthand panel of the Cases page).
Icon fill color in other pedigree members indicates the presence or absence of the proband's phenotypes in a present sample (regardless of the potential presence of additional unrelated phenotypes):
2. Icon color intensity denotes whether sample files have been uploaded for the particular individual:
3. Icon line type indicates whether the sample is considered or excluded during analysis (relevant to samples with uploaded files only):
Add new case page > Family tree screen > Add patient information panel > Patient info section
Note: The fields marked with (*) are mandatory.
Note: Please omit the Patient ethnicities field for non-proband samples.
Options: Male, Female, Unknown.
Indicates the family relationship of a subject to the Proband automatically inferred from the pedigree. Options: Father, Mother, Sibling, Child, Other.
Expected format: mm/dd/yyyy.
Mark the checkbox if you want to exclude the sample from the AI Shortlist analysis and Inheritance filters while preserving genotype data.
If a sample shares some phenotypes with the Proband, you can copy them by checking this box. Proband's phenotypes will appear in a newly created Related Phenotypes section. To remove any of the proband's phenotypes not observed in a current individual, click the ☒ button next to the HPO term in the Related Phenotypes section.
Note: A popup notification will appear at the bottom of the page if any input HPO term or HPO ID is unknown.
Phenotypes not shared with a Proband. They can be added one by one () or in batch ().
Please follow the steps described below for each phenotype:
Enter an HPO term (e.g., Hypoplasia of the ulna), an HPO ID (e.g., HP:0003022), or a descriptive phenotype name (e.g., Underdeveloped ulna) in the search box;
Select a matching term from a dropdown menu and press Complete after you've added all the terms.
Paste a list of comma-separated HPO terms or HPO IDs in the search box and press Complete.
This guide provides a step-by-step process for creating a new case via the user interface. Detailed instructions for each step are available in the corresponding pages of the .
Caution: Please note that refreshing or leaving the page, exiting the Add new case tab, or power failure of your computer before you've completed adding a new case will result in loss of the case creation progress.
> Family tree screen > Add patient information panel > Add sample section
You can choose one of the following options:
Existing sample: Pick one of the samples already loaded on the platform
Upload new sample: Upload files from your PC and enter sample name
While creating a new case, you can choose whether to include secondary findings for the proband. This option is available on the Family Tree screen → Create family tree panel → Show Secondary Findings.
Secondary findings are genetic variants that are not related to the primary indication for testing but may have important medical implications. These variants are automatically assigned the Incidental tag when they meet American College of Medical Genetics and Genomics (ACMG)-defined criteria for reportable secondary findings.
In Emedgene, the terms incidental findings and secondary findings both refer to ACMG-defined secondary findings
Choose from storage: Choose files from your cloud storage and enter sample name
No sample: Postpone uploading files but proceed with case creation or skip uploading files for family members other than Proband
The Add New Case flow does not validate that sample IDs are unique or that input files are uncorrupted. Please ensure sample IDs are unique and that input files are valid before creating the case.
A case won't run if Proband sample files are missing. However, sample files are not mandatory for the rest of the family members (although highly recommended).
When choosing an existing file path, the samples used may be cached from the original run. For a top-up flow please use a new file path.
When you are loading sample files from your PC or choosing them from the storage, and there is more than one file per sample, please ensure that all the necessary files are simultaneously selected in the upload pop-up. You may only select one file type per case (i.e. you may not select both a .vcf and a .bam at the same time).
* Filled - the individual is affected by all of the proband's phenotypes;
* Half-filled - the individual is affected by some of the proband's phenotypes;
* Empty - the individual is not affected by any of the proband's phenotypes.* Full color - the sample has files loaded in the case;
* Faded color - no sample files are available.* Solid - the sample is included in the analysis;
* Dashed - the sample is ignored by Inheritance filters and the AI Shortlist algorithm, but you still can explore its genotypes.\
Click on the Add New Case button on the top navigation panel.
At the Select sample type page, choose the file type for your case analysis (FASTQ, gVCF, VCF, or Array).
Click Next to proceed.
The page is divided into two panels: Create family tree (left) and Add patient information (right).
Use the visual tool to build the pedigree.
Add Clinical Notes (optional) in free text, or upload a clinical presentation file (.pdf, .xls, .txt, .doc, .jpeg, .jpg).
HPO terms for phenotypes and diseases will be extracted and can be linked to the proband.
Select suspected Inheritance mode(s) (for record only; not used in the analysis).
Decide whether to include Secondary findings in the proband for the AI Shortlist (checkbox).
For each family member:
Add a sample (use a unique file path unless reusing samples).
The Add New Case flow does not validate that sample IDs are unique or that input files are uncorrupted. Please ensure sample IDs are unique and that input files are valid before creating the case.
If a QC metrics file (metrics.tar.gz) is uploaded from BSSH, it will not be processed.
Keep file names under 255 characters and avoid spaces or parentheses in file paths.
Always ensure sample IDs are unique to prevent case failure.
If using joint gVCF input, place the proband first for accurate insufficient region calculation.
The UI does not allow reusing the same gVCF file for multiple samples.
Fill in a sample name (for VCF input, this must match the header in the file).
Complete the required patient details: for a proband and for non-proband samples.
Some diseases may not suggest phenotypes automatically if the source database does not provide them. You can add phenotypes manually in these cases.
Click Next to proceed to the Case info screen.
Here you define how the analysis will run:
Case type: Choose Array, Custom Panel, Exome, Whole Genome, or Other.
For Exome cases, variants outside exons ±50 bp are automatically filtered.
Carrier Analysis: Optional checkbox. Requires a targeted gene list.
:
Select an enrichment kit (if applicable) or "No kit".
If provided, kit details (Lab, Machine, Reagents, Expected coverage) will be used to compare coverage depth and breadth.
If no kit is provided, RefSeq coding regions will be used as reference.
options:
All genes
Phenotype-based genes
Existing gene list
: Select the Preset group appropriate for this case type.
If none is selected, the default Preset group is applied automatically (marked as default).
Consent: Confirm subject consent for extended sharing.
Note: Combining/merging gene lists from the Add New Case UI is supported only via the UI — this is not available from the API or batch upload.
Additional case info (optional):
Indication for testing (free text).
Labels (choose from predefined organization labels; these cannot be changed later).
At the Summary stage, confirm case type, gene list, and other selections.
Caution: Clicking Next here will finalize case creation. After delivery, only the proband’s phenotypes can be edited without reanalysis.
After the case is created:
The Case ID is displayed.
You may add participants so colleagues receive notifications on status changes or updates.
Note: In Illumina Cloud environments, users may still appear as available participants even after being removed from an IAM workgroup. These users do not have access to Emedgene, and accidental adding them as participants to a case does not pose any security or access risk.
A variant is automatically tagged as a secondary finding if it meets all of the following criteria:
Classification: Previously classified as pathogenic or likely pathogenic in ClinVar or Curate variant databases
Zygosity: Heterozygous or homozygous (only homozygous for the HFE gene)
Allele frequency: Less than 5%
Read depth: 10× or higher
Variant quality: Any value except LOW
Affected gene: Listed in the ACMG SF v3.2 or 3.3 medically actionable gene list for reporting secondary findings in clinical exome and genome sequencing (PMID: 37347242, 40568962)
ACTA2, ACTC1, ACVRL1, APC, APOB, ATP7B, BAG3, BMPR1A, BRCA1, BRCA2, BTD, CACNA1S, CALM1, CALM2, CALM3, CASQ2, COL3A1, DES, DSC2, DSG2, DSP, ENG, FBN1, FLNC, GAA, GLA, HFE, HNF1A, KCNH2, KCNQ1, LDLR, LMNA, MAX, MEN1, MLH1, MSH2, MSH6, MUTYH, MYBPC3, MYH11, MYH7, MYL2, MYL3, NF2, OTC, PALB2, PCSK9, PKP2, PMS2, PRKAG2, PTEN, RB1, RBM20, RET, RPE65, RYR1, RYR2, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SMAD3, SMAD4, STK11, TGFBR1, TGFBR2, TMEM127, TMEM43, TNNC1, TNNI3, TNNT2, TP53, TPM1, TRDN, TSC1, TSC2, TTN, TTR, VHL, WT1.
Includes all v3.2 genes plus newly added genes:
PLN
ABCD1
CYP27A1
This brings the total to 84 reportable genes.
Historical note
When Emedgene was first released, the term “incidental findings” was adopted in alignment with the clinical genomics standard at the time. The 2013 ACMG recommendations defined incidental findings as “the results of a deliberate search for pathogenic or likely pathogenic alterations in genes that are not apparently relevant to a diagnostic indication for which the sequencing test was ordered” (PMID: 23788249).
As the field evolved, the ACMG and broader clinical community began to distinguish between “incidental findings” (unexpected, not actively sought) and “secondary findings” (intentionally analyzed and reportable). This shift was reflected in the updated 2016 ACMG guidance (PMID: 27854360).
To reflect this change, Emedgene introduced the term “secondary findings” into the platform. However, “incidental findings” remains in use throughout the platform for technical consistency.
Tips:
Enable secondary findings when clinically relevant — this ensures variants in actionable genes are surfaced automatically.
Always review findings in the context of patient consent and your institution’s reporting policies.
Warnings:
Secondary findings are limited to the ACMG-defined gene lists. Variants outside these lists will not be tagged automatically.
Only variants with adequate sequencing depth and quality are tagged. Low-quality calls may require manual review.
The ethnicities of the proband's mother and father can be specified during the process of UI or API case creation. Please refer to the following list of supported ethnicities.
A region of interest (ROI) BED file determines which genomic regions will be included in the variant analysis. It functions as a preprocessing filter, determining which variants proceed to annotation and interpretation.
If no custom ROI BED kit is applied to a case, the system applies a default ROI BED file based on the case type. All default ROI BED files are available for download (see
Create a new gene list
You may combine multiple gene lists into one, or add specific genes to an existing list during case creation. The merged list behaves like any other list in the platform.
M "Maasai" "Malayali Indian" "Melanesian" "Mesoamerican and Andean" "Mexican American" "Middle Eastern" "Mongolian / Manchurian" "Mormon" "Moroccan" "Moroccan Jews" "Muslim Arab"
N "Native American" "Nepali" "Nigerian" "North African" "North and West European" "Northern Asian" "Northern Indian"
O "Other Pacific Islander"
P "Pakistani" "Papuan" "Polynesian" "Portuguese in Northern Brazil" "Portuguese in Southern Brazil"
R "Russian Jews" "Russians"
S "Samaritan" "Samoan" "Sardinian" "Saudi" "Scandinavian" "Senegambian / Guinean" "Siberian" "Somali" "South African" "South Asian" "Southern East African / Congolese" "Southern European" "Southern Indian" "Southern Indian / Sri Lankan" "Southern South Asian" "Spaniards" "Spanish Jews" "Sub-Saharan African" "Sudanese" "Swedes" "Syrian Jews" "Syrian-Lebanese"
T "Tajikistan Jews" "Thai / Cambodian / Vietnamese" "Tunisian" "Tunisian Jews" "Turkish" "Turkish / Anatolian" "Turkish Jews"
U "Ukraine" "Ukraine Jews" "Uzbekistan/ Bukharan Jews"
V "Venezuela"
W "West African"
Y "Yemenite" "Yemenite Jews"
A "Afghan Jews" "Afghani" "African" "African American" "Afro-Brazilian" Alaska Native" "Algerian" "Algerian Jews" "Amish" "Anatolian" "Arab" "Argentinian/Paraguayan" "Armenian" "Ashkenazi Jews" "Asian" "Asian Brazilian" "Australian Native" "Azerbaijan Jews"
B "Bedouin" "Bengali/Northeast Indian" "British/Irish" "Bulgarian Jews"
C "Caribbean Australian"
"Caucasus Jews" "Central African" "Central Asian" "Chilean" "Chinese" "Chinese Dai" "Christian Arab" "Circassian" "Colombia"
D "Druze" "Dutch"
E "East African" "East Asian" "East European" "Egyptian" "Egyptian Jews" "Emirates" "Ethiopia" "Ethiopian / Eritrean" "Ethiopian Jews" "Ethiopian Jews - Beta Israel" "European" "European American"
F "Fijian Australian" "Filipino" "Filipino Austronesian" "Finnish" "French" "French Canadian"
G "Georgian Jews" "Germans" "Ghanaian / Liberian / Sierra Leonean" "Greece Jews" "Greek Americans" "Greek / Balkan" "Guam/Chamorro"
H "Hawaiian"
I "Iberian" "India - Bene Israel Jews" "India - Cochin Jews" "Indian" "Indigenous Amazonian" "Indigenous peoples in Canada" "Indonesian" "Inuit" "Iranian" "Iranian Persian Jews" "Iraq" "Iraqi Jews" "Irish" "Italian" "Italian Americans" "Italian Jews"
J "Japanese" "Japanese Brazilian" "Jordan"
K "Kenyan" "Korean" "Kurdish" "Kurdish Jews"
L "Latino/Hispanic Americans" "Lebanese Jews" "Levantine" "Libyan" "Libyan Jews"
Research Genome
None
Whole Genome
Exome
Custom Panel
A wide range of genomic regions BED file. It contains:
"RefSeq ALL" transcripts and "GENCODE" full genes regions with 5Kbp upstream and 5Kbp downstream
Within this range, all “Clinical Regions” are included
All dosage regions (HI/TS sig level 1, 2 or 3)
Moreover, liftover versions of both reference regions were included, for the current and previous range versions.
Liftover done using CrossMap (v0.5.2), chain hg19ToHg38.over.chain.gz
NCBI RefSeq regions are based on the release 105 (hg19) and 110 (hg38)
Gencode regions are based on the release V19 (hg19) and V41 (hg38)
All microRNA genes based on HGNC miRNA definition December 2022
ClinGen Dosage region Dec 2022
Promoters from EPDnew human version V6
mtDNA CRS
RNA disease genes based on OMIM and HGNC (Dec 2022): ATXN8OS, TERC, IL12A-AS1, FAAHP1, NUTM2B-AS1, GAS8-AS1, RNU12, MIR204, IGHG2, SLC7A2-IT1, MIR99A, RMRP, XIST, MEG3, DIRC3, MIR17HG, GNAS-AS1, LRTOMT, LINC00299, DUX4L1, MIR137, MIR140, MIR605, SNORD118, RNU4ATAC, HELLPAR, IGHG1, IGHM, MIR19B1, RNU7-1, LINC00237, MIR2861, MIR4718, IGHV3-21, IGHV4-34, IGKC, KCNQ1OT1, MIR184, MIR96, H19, HYMAI, PCDHA9, UGT1A1, AFG3L2P1, DISC2, SNORA31, TRU-TCA1-1, PCDHGA4, TRAC, ECEL1P3, MIAT
ClinVar variants (ClinVar Dec 2022) with any pathogenic or likely pathogenic significance (and some drug responses that are affiliated with pathogenicity)
50K STR regions based on the DRAGEN 4.0 Specification file
CNV variants are not confined to regions of interest.
Download files used in v100.39.0+
Download files used up to v38.0
This is a BED file that includes every clinically relevant region. The following are included:
“RefSeq Curated” and “GENCODE” regions with flanking areas of 50bp from each side 5UTR and 3UTR region for protein coding genes (based on RefSeq)
OMIM disease-related RNA genes (flanking 50bp)
All Clinvar Pathogenic variants regions (flanking 50bp)
Promoters region (EPDnew human version 006, flanking 50bp)
Known STR regions (DRAGEN 4.0 specification file)
All microRNA genes (flanking 50bp based on HGNC)
Full mtDNA region
For consistency, the GRCh38 version includes the lifted over regions of GRCh37 (liftover using CrossMap).
CNV variants are not confined to regions of interest.
Download files used in v100.39.0+
Download files used up to v38.0
BED files defining custom kits can be added in Organization settings > Kit management. Furthermore, the BED file chosen here is linked to a PON (Panel of Normals) file when starting from FASTQs and conducting CNV calling.
After selecting a coverage BED file, the available reference sequences for this kit will be displayed.
Specify details such as laboratory name, sequencing machine used, sequencing reagent kit, and expected coverage.
Options: Male, Female, Unknown.
Handling a proband sample with unknown sex
When a sample is user-assigned "Unknown" sex, the system assumes "Female". This affects CNV interpretation on sex chromosomes in case the genetic sex is actually male:
Chromosome X: CN = 2 is considered reference (REF) for a female genome, so CNVs with two copies are hidden by default. This may cause chromosome X duplications to be missed.
Chromosome Y: CN = 0 is considered reference (REF) for a female genome, so CNVs with zero copies are hidden by default. This may cause chromosome Y deletions to be missed.
To include these variants in the analysis, enable the in Workbench & Pipeline Settings.
The default fixed value for Proband is Test Subject.
Expected format: mm/dd/yyyy.
Options: Affected, Healthy.
The default value for Proband is Affected, but you may change it to Healthy.
To add all relevant phenotypes for the Proband, use one of the following methods:
Automatically infer disease-associated phenotypes (see below).
Notes:
The maximum permissible number of proband phenotypes is 100.
Some diseases may not suggest phenotypes automatically if the source database does not provide them. You can add phenotypes manually in these cases.
Warning: Select valid HPO phenotypic abnormality terms
When adding patient phenotypes, ensure that all selected HPO terms originate from the “Phenotypic abnormality (HP:0000118)” branch of the HPO ontology. Terms outside this branch are not supported for case analysis, as they do not represent clinical phenotypes and may lead to incomplete or inaccurate downstream results.
Please follow the steps described below for each phenotype:
Enter an HPO term (e.g., Hypoplasia of the ulna), an HPO ID (e.g., HP:0003022), or a descriptive phenotype name (e.g., Underdeveloped ulna) in the search box.
Select a matching term from a dropdown menu and press Complete after you've added all the terms and additional patient information below.
Paste a list of comma-separated HPO terms or HPO IDs in the search box and press Complete.
Notes:
A popup notification will appear at the bottom of the page if any input HPO term or HPO ID is unknown.
Only phenotypes from the 'Phenotypic abnormality' HPO branch are currently supported.
In the Clinical Notes section upload a description of the clinical presentation in .pdf, .xls, .txt, .doc, .jpeg, or .jpg format. Among the extracted HPO terms for Phenotypes and Diseases select the ones you want to add to Proband's Phenotypes.
Enter the disease name in the search box, select a matching term from a dropdown menu and press Complete. All the associated phenotypes will be automatically added to the Proband Phenotypes.
Selecting a disease only fetches its associated phenotypes for convenience—it does not affect downstream analysis. You can edit this list to match the proband’s clinical presentation. Only the phenotypes you keep or add influence analysis, not the disease selection itself.
To remove any phenotype described for the disease but not observed in your patient, click the button next to the HPO term in the Proband Phenotypes list.
Note:
Searching for a disease name may return several entries with the same title.
This happens because the disease appears in multiple gene–disease sources, each with its own identifiers and evidence associations. These entries are not merged automatically, so choosing different items may return different sets of phenotypes.
Enter the suspected disease penetrance as a percentage.
Select the appropriate category to indicate the severity of the disease symptoms observed in the patient: Mild, Moderate, Severe, Profound.
Mark the checkbox if applicable.
Note: If consanguinity is identified in the Proband's parents, but this box is not selected in case creation, this will result in a discrepancy alert in the Lab tab.
Paternal and Maternal. Enter the ethnicity name in the search box and select a matching term from a dropdown menu.
