Monday, May 9, 2016

Better summaries of variant information convey the most important information at a glance

We’ve made significant improvements to the information we display on the Variant pages of the T2D Knowledge Portal. The summary at the top of each Variant page (view an example) now shows the reference nucleotide and the variant nucleotide at that position. Transcripts covering the variant are listed, along with several important details for each transcript: the change caused by the variant in the encoded protein sequence (if applicable); the Sequence Ontology term describing the consequence of the variation (for example, “missense variant”); and the expected effect of the variant on protein function, as predicted by the PolyPhen and Sift algorithms.

Summary section of the Variant page

Just below the summary on the Variant page, we’ve also improved the graphic showing the association of the variant with T2D and related traits. We’ve re-named this section “associations at a glance” because it immediately shows the most important information about these associations. 

At-a-glance section of the Variant page. Click the image to view a larger version.

The boxes in this graphic represent the associations of this variant with T2D (at the top) and with other traits (below, in an expandable section). Under the hood, the software is now pulling up information more quickly so that the display is more responsive. We’ve also made it more pleasant to look at, tidying up the shape of the boxes and the alignment of the information they contain.

But beyond the style improvements, we’ve added a lot of substance. Where available, each association now includes the odds ratio (for dichotomous traits) or the effect size (for continuous traits) and the direction of effect. Positive effects are shown in blue, and negative effects in purple. 

We’ve also added the sample size, in black text in the bottom left corner of the box, for each data set. This indicates the total number of individuals involved in the study. And if available, the frequency and count of the variant in the data set are shown in red and blue text at the bottom middle and bottom right corner of the box, respectively. The count indicates the number of haplotypes in the set that contain the variant, while the frequency indicates the occurrence of the variant allele in the sampled population.

This additional information can help you evaluate the significance of associations. The sample size and variant count determine the power of the data set to establish the association. The higher the power, the more accurate the estimate of the variant’s effect.

Finally, when a variant is associated with other traits in addition to T2D, those traits in the same category are labeled with the same color. For example, in the display above, proinsulin levels, fasting glucose, HOMA-B, and two-hour glucose—all glycemic phenotypes—are labeled in orange, while triglycerides, LDL cholesterol, and cholesterol—lipid phenotypes—are labeled in red. This lets you see easily when a variant is linked to multiple traits that could reflect a common process or pathway, possibly offering a clue to the mechanism by which it affects physiology.

So this improved graphic now gives you an idea, literally at a single glance, of how strongly a variant is associated with T2D, how significant that association is, and whether it is also associated with other traits. 

We made these improvements in response to suggestions from scientists who use the T2D Knowledge Portal. We hope to hear your feedback too!

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