Uploaded June 2026 | Updated September 2026, 2 hours ago
If your rare disease research workflow stalls after short-read or tiered assays, HiFi long-read sequencing can add variant, methylation, and phasing evidence.
In this PacBio webinar, Nina Gonzaludo, PhD, and Ramakrishnan (Ramki) Rajagopalan, PhD, from the Children's Hospital of Philadelphia, connect that workflow question to CHOP research cohort examples involving NIPBL insertions, a MEG3 deletion with methylation and phasing evidence, and Iso-Seq transcript evidence near HK1.
*Key takeaways*
- Why rare disease research workflows can leave structural variants, repeat insertions, phasing relationships, methylation patterns, and transcript effects unresolved.
- What published rare disease studies show about HiFi WGS, including variant classes, methylation patterns, phasing, and workflow questions that are difficult to interpret with staged short-read and assay-specific approaches.
- How HiFi long-read sequencing supports research into SNVs, indels, CNVs/SVs, tandem repeats, methylation, and phasing in one data type.
- CHOP cohort examples involving NIPBL insertion events, a 203 bp MEG3 deletion phased with a nearby SNV, and an HK1 upstream duplication explored with PacBio Iso-Seq.
- Q&A on when to consider long reads earlier, mitochondrial DNA workflows, methylation tissue specificity, targeted versus genome-wide approaches, and 20x versus 30x coverage tradeoffs.
*Featured speakers*
- Nina Gonzaludo, PhD, Global Segment Lead - Clinical, Rare Disease, PacBio
- Ramakrishnan (Ramki) Rajagopalan, PhD, Director of Translational Bioinformatics, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
*Chapters*
00:00 Welcome and webinar setup
01:33 Rare disease research workflows and why more complete data matters
02:49 HiFi sequencing overview for rare disease research
03:55 Rare disease study examples using HiFi whole genomes
09:50 Multiomic applications: Iso-Seq, methylation, and targeted sequencing
14:09 PacBio WGS variant pipeline and scale
17:11 Ramki Rajagopalan introduces CHOP and study goals
19:47 Clinical testing context and research workflow boundaries
20:30 Why tiered assays persist in practice
25:22 Gaps in staged rare disease research workflows
30:06 Small insertion and phasing in an unresolved sample
31:36 NIPBL insertions in Cornelia de Lange syndrome research
34:53 Multiomics examples from CHOP
37:22 MEG3 deletion, methylation, and Kagami-Ogata syndrome
40:23 Iso-Seq and HK1 transcript evidence
42:47 Barriers to bringing long reads toward lab implementation
45:07 Q&A: selecting samples for long-read sequencing
48:44 Q&A: multiomics, methylation, and RNA
50:00 Q&A: mitochondrial DNA and heteroplasmy
52:10 Q&A: methylation signatures and tissue specificity
53:02 Q&A: targeted versus genome-wide approaches
54:49 Q&A: coverage and variant calling tradeoffs
56:19 Q&A: downstream research follow-up and future progress
*Resources:*
- HiFi sequencing technology: pacb.com/technology/hifi-sequencing
- Rare disease HiFi sequencing whitepaper: pacb.com/wp-content/uploads/Whitepaper-Improving-solve-rates-in-rare-disease-research-with-HiFi-long-read-sequencing.pdf
- Long-read RNA-seq in rare disorders: pacb.com/publications/hifi-long-read-rna-sequencing-enhances-clinical-diagnostics-in-rare-disorders
Where would long-read data add the most value in your rare disease research workflow?
*Comment below.*
*Subscribe to PacBio for more webinars on HiFi sequencing, rare disease research, human genomics, and multiomic applications:*
youtube.com/@PacificBiosciences?sub_confirmation=1
For Research Use Only. Not for use in diagnostic procedures.
#RareDisease #HiFiSequencing #LongReadSequencing
If your rare disease research workflow stalls after short-read or tiered assays, HiFi long-read sequencing can add variant, methylation, and phasing evidence.
In this PacBio webinar, Nina Gonzaludo, PhD, and Ramakrishnan (Ramki) Rajagopalan, PhD, from the Children's Hospital of Philadelphia, connect that workflow question to CHOP research cohort examples involving NIPBL insertions, a MEG3 deletion with methylation and phasing evidence, and Iso-Seq transcript evidence near HK1.
*Key takeaways*
- Why rare disease research workflows can leave structural variants, repeat insertions, phasing relationships, methylation patterns, and transcript effects unresolved.
- What published rare disease studies show about HiFi WGS, including variant classes, methylation patterns, phasing, and workflow questions that are difficult to interpret with staged short-read and assay-specific approaches.
- How HiFi long-read sequencing supports research into SNVs, indels, CNVs/SVs, tandem repeats, methylation, and phasing in one data type.
- CHOP cohort examples involving NIPBL insertion events, a 203 bp MEG3 deletion phased with a nearby SNV, and an HK1 upstream duplication explored with PacBio Iso-Seq.
- Q&A on when to consider long reads earlier, mitochondrial DNA workflows, methylation tissue specificity, targeted versus genome-wide approaches, and 20x versus 30x coverage tradeoffs.
*Featured speakers*
- Nina Gonzaludo, PhD, Global Segment Lead - Clinical, Rare Disease, PacBio
- Ramakrishnan (Ramki) Rajagopalan, PhD, Director of Translational Bioinformatics, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
*Chapters*
00:00 Welcome and webinar setup
01:33 Rare disease research workflows and why more complete data matters
02:49 HiFi sequencing overview for rare disease research
03:55 Rare disease study examples using HiFi whole genomes
09:50 Multiomic applications: Iso-Seq, methylation, and targeted sequencing
14:09 PacBio WGS variant pipeline and scale
17:11 Ramki Rajagopalan introduces CHOP and study goals
19:47 Clinical testing context and research workflow boundaries
20:30 Why tiered assays persist in practice
25:22 Gaps in staged rare disease research workflows
30:06 Small insertion and phasing in an unresolved sample
31:36 NIPBL insertions in Cornelia de Lange syndrome research
34:53 Multiomics examples from CHOP
37:22 MEG3 deletion, methylation, and Kagami-Ogata syndrome
40:23 Iso-Seq and HK1 transcript evidence
42:47 Barriers to bringing long reads toward lab implementation
45:07 Q&A: selecting samples for long-read sequencing
48:44 Q&A: multiomics, methylation, and RNA
50:00 Q&A: mitochondrial DNA and heteroplasmy
52:10 Q&A: methylation signatures and tissue specificity
53:02 Q&A: targeted versus genome-wide approaches
54:49 Q&A: coverage and variant calling tradeoffs
56:19 Q&A: downstream research follow-up and future progress
*Resources:*
- HiFi sequencing technology: pacb.com/technology/hifi-sequencing
- Rare disease HiFi sequencing whitepaper: pacb.com/wp-content/uploads/Whitepaper-Improving-solve-rates-in-rare-disease-research-with-HiFi-long-read-sequencing.pdf
- Long-read RNA-seq in rare disorders: pacb.com/publications/hifi-long-read-rna-sequencing-enhances-clinical-diagnostics-in-rare-disorders
Where would long-read data add the most value in your rare disease research workflow?
*Comment below.*
*Subscribe to PacBio for more webinars on HiFi sequencing, rare disease research, human genomics, and multiomic applications:*
youtube.com/@PacificBiosciences?sub_confirmation=1
For Research Use Only. Not for use in diagnostic procedures.
#RareDisease #HiFiSequencing #LongReadSequencing
