Uploaded August 2026 | Updated September 2026, 19 minutes ago
How can HiFi long-read sequencing help you study ALS genetics when short-read data struggles to resolve C9orf72 repeat expansions and structural variants?
In this PRISM 2026 presentation, Amy Easton from Target ALS and Evan Udine from Mayo Clinic show how the Target ALS Data Engine, AGRI, and PacBio HiFi sequencing are being used to build open multi-omic resources for ALS research, size C9orf72 repeats that short reads can underestimate, and examine repeat-expansion biology.
*Key takeaways*
- Target ALS is building an openly shared HiFi sequencing collection for ALS, with 420 people enrolled in AGRI and a goal of 6,000 long-read whole genomes.
- AGRI includes at least 30% participants from diverse ethnic, genetic, and demographic backgrounds, supporting variant discovery beyond existing catalogs.
- Early AGRI analysis found a 6% increase in variants in people of European descent and a 16% increase in people of non-European descent versus catalogues like gnomAD.
- In C9orf72 examples, long-read data detected repeat lengths about two- to five-fold longer than short-read data.
- Evan Udine shows how WGS, TRGT, PureTarget, and Iso-Seq can help study C9orf72 repeat length, methylation, penetrance, and disease modifiers.
*Featured speakers*
- Amy Easton, VP, Scientific Programs (Target ALS)
- Evan Udine, Postdoctoral Fellow - Neuroscience (Mayo Clinic, Target ALS)
*Chapters*
00:00 Target ALS and missing ALS heritability
00:42 ALS overview and 90% unknown cause
02:05 Lessons from ALS genetics
03:07 Building the Target ALS Data Engine
03:50 Why HiFi sequencing for ALS genetics?
04:25 AGRI and postmortem tissue cohorts
06:07 Sequencing methods and QC metrics
07:36 Early AGRI findings: variants and structural variation
08:52 C9orf72 repeat length and methylation
10:28 Target ALS summary and acknowledgements
11:14 Evan Udine on C9orf72 repeat expansion
11:41 Target ALS C9orf72 disease drivers consortium
12:07 C9orf72 repeat biology and penetrance
13:41 Southern blotting, short reads, and methylation assays
14:49 Why HiFi sequencing for C9 repeat-expansion research?
15:17 WGS from 14 C9orf72 expansion carriers
15:40 Detecting and sizing the repeat expansion
16:54 Finding modifiers outside C9
17:48 Targeted sequencing and PureTarget
20:04 Long-read RNA sequencing and Iso-Seq
20:58 Summary: C9 penetrance and genetic modifiers
21:38 Closing
*Resources*
- Target ALS Data Engine: targetals.org/research/genomic-datasets
- PacBio HiFi sequencing: pacb.com/technology/hifi-sequencing/how-it-works
- PacBio Revio system: pacb.com/revio
- PacBio PureTarget: pacb.com/technology/puretarget
- PacBio Kinnex: pacb.com/technology/kinnex
Which ALS genetics question would you prioritize first: C9 repeat length, methylation, or genome-wide modifiers? Comment below.
*Subscribe for more PacBio genomics content:*
youtube.com/@PacificBiosciences?sub_confirmation=1
Learn more about PacBio at pacb.com
Legal & Trademarks: pacb.com/legal-and-trademarks
For Research Use Only. Not for use in diagnostic procedures.
#ALSResearch #HiFiSequencing #LongReadSequencing
How can HiFi long-read sequencing help you study ALS genetics when short-read data struggles to resolve C9orf72 repeat expansions and structural variants?
In this PRISM 2026 presentation, Amy Easton from Target ALS and Evan Udine from Mayo Clinic show how the Target ALS Data Engine, AGRI, and PacBio HiFi sequencing are being used to build open multi-omic resources for ALS research, size C9orf72 repeats that short reads can underestimate, and examine repeat-expansion biology.
*Key takeaways*
- Target ALS is building an openly shared HiFi sequencing collection for ALS, with 420 people enrolled in AGRI and a goal of 6,000 long-read whole genomes.
- AGRI includes at least 30% participants from diverse ethnic, genetic, and demographic backgrounds, supporting variant discovery beyond existing catalogs.
- Early AGRI analysis found a 6% increase in variants in people of European descent and a 16% increase in people of non-European descent versus catalogues like gnomAD.
- In C9orf72 examples, long-read data detected repeat lengths about two- to five-fold longer than short-read data.
- Evan Udine shows how WGS, TRGT, PureTarget, and Iso-Seq can help study C9orf72 repeat length, methylation, penetrance, and disease modifiers.
*Featured speakers*
- Amy Easton, VP, Scientific Programs (Target ALS)
- Evan Udine, Postdoctoral Fellow - Neuroscience (Mayo Clinic, Target ALS)
*Chapters*
00:00 Target ALS and missing ALS heritability
00:42 ALS overview and 90% unknown cause
02:05 Lessons from ALS genetics
03:07 Building the Target ALS Data Engine
03:50 Why HiFi sequencing for ALS genetics?
04:25 AGRI and postmortem tissue cohorts
06:07 Sequencing methods and QC metrics
07:36 Early AGRI findings: variants and structural variation
08:52 C9orf72 repeat length and methylation
10:28 Target ALS summary and acknowledgements
11:14 Evan Udine on C9orf72 repeat expansion
11:41 Target ALS C9orf72 disease drivers consortium
12:07 C9orf72 repeat biology and penetrance
13:41 Southern blotting, short reads, and methylation assays
14:49 Why HiFi sequencing for C9 repeat-expansion research?
15:17 WGS from 14 C9orf72 expansion carriers
15:40 Detecting and sizing the repeat expansion
16:54 Finding modifiers outside C9
17:48 Targeted sequencing and PureTarget
20:04 Long-read RNA sequencing and Iso-Seq
20:58 Summary: C9 penetrance and genetic modifiers
21:38 Closing
*Resources*
- Target ALS Data Engine: targetals.org/research/genomic-datasets
- PacBio HiFi sequencing: pacb.com/technology/hifi-sequencing/how-it-works
- PacBio Revio system: pacb.com/revio
- PacBio PureTarget: pacb.com/technology/puretarget
- PacBio Kinnex: pacb.com/technology/kinnex
Which ALS genetics question would you prioritize first: C9 repeat length, methylation, or genome-wide modifiers? Comment below.
*Subscribe for more PacBio genomics content:*
youtube.com/@PacificBiosciences?sub_confirmation=1
Learn more about PacBio at pacb.com
Legal & Trademarks: pacb.com/legal-and-trademarks
For Research Use Only. Not for use in diagnostic procedures.
#ALSResearch #HiFiSequencing #LongReadSequencing
