Admixed populations, and strategies for nanopore data analysis

David Eccles is a freelance bioinformatician based at the Malaghan Institute
for Medical Research in Wellington, New Zealand. He has working on various
topics related to human genetics; co-wrote the Trinity De-novo RNA Sequence
assembly program while based at the Max Planck Institute in Muenster,
Germany; is an active member of the MinION Analysis and Reference
Consortium, an international group exploring methods and applications for
Oxford Nanopore data; and recently spoke on “Sequencing that stimulates the
sensors” at a TEDxWellington event.
David will be available to meet with interested researchers during the day.

Estimation of Genomic Ancestry in Admixed Populations – David Eccles, Geoff Chambers, Rod Lea

The native Maori settlement of New Zealand about 600 years ago
represents an end-point of a long journey of island-hopping voyages
across vast stretches of open sea — the last of the great human
migrations. Nearly 250 years ago, European settlers discovered this
remote island country in the South Pacific, and thus began the mixing
of two cultures that were literally oceans apart.

The Maori population of today presents an exciting opportunity to
study recent ancestral population admixture. A bootstrap sub-sampling
method was utilised to generate a set of group-specific markers for
the investigation of admixture within an iwi (Maori tribe) from Hawkes
Bay, New Zealand. A validated set of 10 markers was constructed that
estimates individual ancestral fraction with high accuracy (median =
98%, IQR = 95-99). These markers were used to determine the variation
of Maori-European ancestral fraction within this tribe, together with
an estimate of the amount of European ancestry in the population

The generation of a panel of validated group-specific markers is
possible even when using a low-density marker set and small sample
group sizes. This method is likely applicable to other genome-wide
studies, and provides one way in which false positive associations
could be quickly excluded from candidate marker sets.

The MinION: New Data; New Analyses – David Eccles

The Oxford Nanopore MinION is unique among DNA sequencing technology,
in that it is the only technology that doesn’t require synthesis in
order to derive a DNA sequence. Instead, sensors detects subtle
changes in the electrical properties of bases, observing single
strands of DNA as they pass through a nanopore.

The novelty of signal-level data produced by the MinION presents new
opportunities for data display and analysis. Over the course of the
last two years, a number of different methods were developed to
represent both signal-level and base-called MinION data. Three of
these methods will be demonstrated:

  • A colour-based visual representation of pairwise alignment
  • Aligning raw sensor data to sequenced bases
  • Turning signal squiggles into sound

The disruptive nature of this new sequencing technology means that
there is plenty of scope for new research and analysis. It is hoped
that by demonstrating a few things that can be done with the
technology, others can be inspired to discover other novel uses for
the device.