End the diagnostic odyssey.
Resolve the unresolved.
When short-read exomes and panels return negative, the search isn't over. Our 4Power WGS HiFi long-read sequencing detects the structural variants, repeat expansions, and complex rearrangements that standard testing misses — delivering molecular answers for your most challenging rare disease cases.
Standard tests leave families stranded
Short-read sequencing (SRS) is cost-effective for basic variant detection, but it struggles with repetitive sequences, large structural variants, and homologous regions — leaving 10–20% of the genome unresolved. For patients with rare genetic disorders, this means initial tests fail to identify causative variants.
The result is a "diagnostic odyssey": years of repeated testing, misdiagnoses, missed treatment windows, and emotional toll on families — especially in consanguineous populations where autosomal recessive disorders are prevalent.
Why long reads change everything
PacBio HiFi sequencing generates reads of 15–25 kb at >99.9% accuracy, enabling de novo assembly, precise phasing, and methylation detection in a single workflow — revealing the variants short reads cannot reach.
Illumina SRS
The standard — powerful, but blind to the hardest regions
- Misses large structural variants & complex rearrangements
- Cannot resolve repeat expansions & STRs
- Fails in homologous regions & pseudogenes
- Limited phasing — cannot determine parental allele
- No native methylation / epigenetic detection
4Power WGS HiFi
Long, accurate reads that see the whole genome
- Detects SVs, CNVs, inversions & complex rearrangements
- Resolves repeat expansions & short tandem repeats
- Spans homologous regions & pseudogenes (e.g. STRC)
- Native phasing — parental allele & de novo determination
- Methylation & imprinting detection in a single run
When standard tests fail, 4Power WGS HiFi delivers answers.
Our flagship whole-genome HiFi test is built specifically for undiagnosed rare disease and complex cancer cases — the patients left without answers after exome, panel, or short-read WGS.
Whole-genome coverage
Coding & non-coding regions — intergenic, intronic, deep intronic variants
All variant classes
SNVs, indels, SVs, CNVs, repeat expansions, mobile element insertions
Trio & proband options
De novo detection with parental phasing for precise inheritance mapping
ACMG-compliant report
Classified variants with clinical interpretation & genetic counseling
Variant classes detected Single Test
A test for every clinical question
From targeted panels to whole-genome HiFi, choose the right depth for your patient's presentation and prior testing history.
4Power WGS HiFi
Whole-genome PacBio HiFi for unresolved cases after negative exome or panel. Detects SVs, repeat expansions, imprinting defects, and complex rearrangements in a single test.
Clinical Exome Sequencing
Comprehensive coding-region analysis for suspected Mendelian disorders. Cost-effective first-line test covering >1,750 disease-associated genes with AI-driven variant prioritization.
Inherited Retinal Dystrophy Panel
Targeted HiFi panel for retinitis pigmentosa, Stargardt, Leber congenital amaurosis & macular dystrophies. Resolves the ~40% of IRD cases unsolved by exome — deep intronic & SV variants.
Newborn WGS HiFi Screening
Early detection of treatable rare diseases from dried blood spots — Pompe, SMA, lysosomal storage disorders, urea cycle defects. Identifies conditions missed by biochemical NBS panels.
Neurodevelopmental & Ataxia Panel
HiFi detection for intellectual disability, autism spectrum, spinocerebellar ataxias, Friedreich ataxia & myotonic dystrophy. Captures repeat expansions invisible to short-read sequencing.
Carrier & Prenatal Screening
Pre-conception carrier screening and prenatal diagnostics for high-risk families. Informed by India-specific population diversity and recurrence-risk counseling for recessive disorders.
More answers, fewer tests
Across global benchmarks and Nucleome's own pipeline, HiFi long-read sequencing consistently outperforms short-read methods on the variants that matter most for rare disease — often replacing multiple complementary tests with a single run.
Source: PacBio benchmark studies & Nucleome Informatics rare disease pipeline (2023–2025).
Diagnostic yield by disease domain — HiFi vs short-read
Cases that short-read could not solve
Real-world examples of how HiFi sequencing delivered molecular diagnoses where standard testing failed — and how Nucleome brings this capability home to Indian families.
Resolving structural variants in NDDs
Eight family trios with children affected by unsolved intellectual disability & autism. Prior SRS exome identified no clear causes.
123-bp intronic duplication in NXPE3 (de novo, neurodevelopment); 303-bp insertion in TAOK3 intron (intellectual disability); multiple de novo repeat expansions disrupting gene regulation.
Repeat expansions in neurodegenerative disease
96 probands with suspected ataxia & dementia, unsolved by SRS trio sequencing. HiFi at ~26× coverage found explanations in 16 cases.
FXN (GAA)n expansion in Friedreich ataxia; CNBP STR expansion in myotonic dystrophy type 2; NF1 mobile element insertion in neurofibromatosis type 1 — all in repetitive/GC-rich regions undetectable by SRS.
Complex rearrangements in hearing & vision loss
19 pediatric patients with unsolved sensorineural hearing loss. HiFi at 24–32× identified causes in 21%, including pseudogene-resistant calls.
Hemizygous OTOA deletion; STRC loss-of-function + CNVs resolved despite pseudogene homology; copy-neutral MITF inversion. In IRDs: deep intronic variants, exon deletions & complex SVs.
Imprinting defects & large-scale cohorts
34 families with suspected autosomal recessive disease, negative after SRS exomes. HiFi at ~10× coverage identified candidates in 38%.
MECP2 inversions causing haploinsufficiency in Rett syndrome-like cases (100,000 Genomes Project); maternal uniparental heterodisomy on chr14 detected via methylation tools — Temple syndrome. Nucleome has diagnosed novel SCN1A mutations in pediatric epilepsy.
A clear path, end to end
We handle the entire journey — from sample collection to clinical report and genetic counseling — so your team can focus on patient care.
Sample Intake
Blood, saliva, or dried blood spot. Trio or proband. Order via DrSeq portal.
HiFi Sequencing
PacBio Revio / Sequel II. 15–25 kb reads, >99.9% accuracy, ~30× coverage.
AI Bioinformatics
Variant calling, phasing, SV/CNV/STR detection, methylation analysis.
Clinical Interpretation
ACMG-compliant variant classification, AI-driven prioritization & curation.
Report & Counseling
Actionable clinical report with genetic counseling & recurrence-risk guidance.
Built for the Indian clinical context
We combine global-grade HiFi infrastructure with deep expertise in India's genetic diversity — reducing reliance on overseas labs and accelerating answers for your patients.
South Asia's first PacBio Revio
We operate the region's most advanced long-read infrastructure — Sequel II & Revio platforms — alongside Illumina and Bionano for hybrid assemblies, ensuring >99% genome coverage.
India-specific genetic diversity
13+ years of clinical expertise with Indian populations — including consanguineous cohorts where autosomal recessive disorders are prevalent. Our reference data reflects the patients you actually see.
ACMG-compliant, actionable reports
Every report follows ACMG variant classification guidelines, with AI-enhanced prioritization and integrated genetic counseling — so results translate directly into clinical decisions.
AI-driven variant prioritization
Custom ML pipelines for SV detection, phasing, and epigenetic insights — turning raw HiFi data into a ranked, clinically interpretable variant shortlist, fast.
End-to-end support
From sample collection to genetic counseling, we support your team at every step — with a web-based ordering portal (DrSeq) designed for clinical workflows.
Cost-effective, in-country
Bringing global HiFi advancements home — reducing reliance on international labs, accelerating turnaround, and making advanced rare disease testing accessible across India.
What referring scientists say
Thank you for providing us with good quality PacBio reads. I am highly satisfied with the quality of services, sequence reads and read length. I am looking forward to many more such sequencing services from your company.
I had a very fruitful discussion regarding the project, and very detailed analysis of the complete pipeline. The team gave useful insights on the data and different ways of analysis. The feedback regarding the quality of the data is encouraging — I am excited by the chromosome-wise distribution.
I would like to appreciate the help we got from the entire team. Being a new explorer in the NGS field, we were not very familiar with the area, but Team Nucleome was helpful and guided us to explore various associated fields. Thank you to Mr. Dushyant and his team.
Questions before you refer
Resolve your next undiagnosed case.
Whether you're tackling a single diagnostic odyssey or building a rare disease program, our clinical team will help you select the right test and guide your patient from sample to answer.