Using BEvariants

Using BEvariantsInstructions for usageNote: For deep learning based prediction of base editing efficiencies for arbitrary sequences, please use DeepBE instead. Gene_Name

Enter a gene name contained within This List of genes, and press the blue Search button.Example Input: A2M (or Load Example) Results

Results are available to filter or sort each column, as well as a Download CSV button below. Download_Load

The results can be interpreted as follows (you may sort or filter each column as adequate):Identifiers and Targets

Base Editor

Meaning: The type of base editor used to edit the single guide RNA (sgRNA) library.
Context: The study used adenine base editors (ABEs) and cytosine base editors (CBEs) to edit sgRNA libraries.

Gene

Meaning: The symbol of the genomic gene targeted by the sgRNA.
Context: The study targeted cancer-related genes found in databases like COSMIC, as well as common essential genes.

Meaning: A unique identifier assigned to the specific sgRNA used in the library.
Context: These identifiers correspond to sgRNAs from various libraries designed to target specific mutations.

Functional Classifications

Classification

Meaning: The functional effect of the mutation on cell proliferation and survival.
Categories: Seven functional classes — Depleting, Likely depleting, Likely neutral (possibly depleting), Neutral, Likely neutral (possibly outgrowing), Likely outgrowing, and Outgrowing — plus Not assessed, the eighth value the column takes, for an sgRNA the libraries did not classify.
Method: Classifications are based on the log-fold change (LFC) of sgRNA abundance and statistical P-values compared to non-targeting controls.

Classification Afatinib

Meaning: The functional effect of the mutation on cell survival in the presence of the EGFR inhibitor afatinib.
Context: This was used to identify mutations conferring resistance (e.g., EGFR p.T790M) or sensitivity to the drug.

Editing Outcomes and Variants

Major alleles of sgRNA

Meaning: The protein variant this sgRNA produces most often, written as an amino acid change (e.g., M1V or P17L) or as a combination of them separated by "/". Not assessed appears where none was called.
Context: It is a property of the sgRNA, so it repeats on every row that sgRNA has, whereas Protein variant names the variant of the row itself. The editors deaminate within specific windows (typically positions 4–7 or 4–8) of the protospacer, so one sgRNA can produce several variants and this column names the predominant one.

Protein variant

Meaning: The specific amino acid change (e.g., p.H312R) resulting from the nucleotide edit.
Context: This represents the intended or observed protein-level mutation.

Primary protein variant

Meaning: A flag, True or False, saying whether this row's variant is the dominant one among the editing outcomes of its sgRNA. The variant itself is in Protein variant.
Definition: A variant is flagged True if its relative frequency among all base-edited non-synonymous variants is greater than 75%.

Nonsynonymous Editing (%)

Meaning: The percentage of sequencing reads containing any mutation that results in an amino acid change.
Significance: sgRNAs with a non-synonymous editing efficiency lower than 60% were generally excluded from functional classification to ensure accuracy.

Frequency Metrics

Frequency of major nonsynonymous variants among total reads (%)

Meaning: The percentage of total sequencing reads carrying this row's protein variant, so it varies from row to row within one sgRNA. On the row whose variant is that sgRNA's major allele it is the frequency of the major variant the heading names.
Context: This measures the overall efficiency of generating that specific mutant within the entire cell population.

Relative frequency of the variant among base-edited nonsynonymous sequences (%)

Meaning: The proportion of the specific variant relative to the total pool of non-synonymous edits.
Significance: This metric is used to determine if an sgRNA produces a "clean" outcome; if this value is >75%, the phenotype is attributed to that single primary variant.

Sample OutputsSample interactive outputs can be immediately obtained by pressing the Load Example button, followed by pressing the Search button at the right of the Gene Name field.ContactIf you have any questions, bug reports, or suggestions, please do not hesitate to contact us through the Support page.

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