At Alstronix Technologies, our Rapid
Whole Genome Sequencing (rWGS) solution is engineered to unlock comprehensive genetic
information with unprecedented speed, reliability, and an acute focus on the
unique and diverse genetic landscape of Indian populations. We understand the
critical need for rapid insights in clinical settings and the imperative for
population-specific accuracy in research.
Whether the application is the urgent
diagnosis of rare genetic disorders, advancing the frontiers of clinical
research, or conducting in-depth ancestry studies, our rWGS pipeline delivers
end-to-end genomic data. This encompasses everything from the raw sequencing
reads generated by cutting-edge platforms to meticulously curated,
high-confidence variant calls and richly annotated insights, ready for
interpretation and action.
What Makes Our rWGS Different?
Alstronix Technologies' rWGS stands
apart due to several key differentiators, each designed to optimize performance
for the Indian genomic context and deliver superior results:
· Optimized for Indian Genomic Diversity: A Population-Specific Advantage
Unlike generic WGS solutions, our
pipeline is built with intrinsic population-specific sensitivity. This means it
is highly adept at capturing rare and ancestry-linked genetic variants that are
crucial within India's diverse gene pools. We specifically address the complex
genetic admixtures found in the subcontinent, including ancestral components
such as Ancestral South Indian (ASI), Ancestral North Indian (ANI), Indus
Valley Civilization (IVC) components, and influences from Steppe and Iranian
ancestries. This optimization ensures a higher detection rate and more accurate
interpretation of variants relevant to Indian individuals, mitigating the
"missing heritability" often observed in studies predominantly based
on European populations.
· Fast Turnaround Time (TAT): Meeting Time-Sensitive Needs
We recognize that in many clinical
and research scenarios, time is of the essence. Our highly efficient
bioinformatics pipeline is meticulously optimized to deliver results with
exceptional speed, without compromising on data quality. From the moment we
receive raw FASTQ data, our streamlined processes ensure rapid progression
through alignment, variant calling, and annotation, culminating in
comprehensive, annotated variant reports in the shortest possible timeframe.
This accelerated TAT is crucial for timely clinical decision-making in rare
disease diagnostics and for maintaining momentum in fast-paced research
projects.
· High-Quality Variant Calling: Precision and Robustness
Accuracy in variant detection is
paramount. Our rWGS pipeline integrates and leverages industry-standard,
gold-standard tools renowned for their robustness and precision in identifying
genetic variations. These include:
o
GATK (Genome Analysis Toolkit): A widely recognized and highly respected suite of tools developed by
the Broad Institute, particularly for germline variant discovery.
o
DeepVariant: A revolutionary deep learning-based variant caller developed by Google,
known for its superior accuracy, especially in challenging genomic regions.
o
SAMtools: Essential for
manipulating sequence alignment data (SAM/BAM files).
o
BWA (Burrows-Wheeler Aligner): A fast and accurate short-read aligner used to map sequencing reads to
a reference genome. This multi-tool approach ensures comprehensive and highly
confident detection of both Single Nucleotide Polymorphisms (SNPs) and small
insertions/deletions (Indels).
· Comprehensive Bioinformatics Pipeline: An End-to-End Solution
Our rWGS solution encompasses a
meticulously designed, end-to-end bioinformatics pipeline, ensuring data
integrity and accurate analysis at every step:
o
Quality Control (QC): Initial assessment of raw sequencing reads using tools like FastQC and aggregated reporting with MultiQC to identify potential issues such as low quality
bases, adapter contamination, or overrepresented sequences.
o
Read Trimming: Removal of low-quality bases and adapter sequences using tools such as Trimmomatic and Cutadapt to improve
downstream alignment accuracy.
o
Alignment: Mapping of cleaned reads to the human reference genome (GRCh38) using BWA (Burrows-Wheeler Aligner).
o
Duplicate Removal: Identification and marking of PCR duplicates using Picard Tools to prevent inflated variant calls due to
amplification biases.
o
Variant Calling: High-confidence variant identification using GATK HaplotypeCaller or DeepVariant.
o
Annotation: Adding functional and clinical context to identified variants using
powerful annotation tools like VEP (Variant Effect Predictor)
from Ensembl and ANNOVAR. This step provides information on gene impact,
amino acid changes, conservation scores, and more.
o
Filtration: Systematic filtering of variants against publicly available databases
such as gnomAD (Genome Aggregation Database) for population allele
frequencies, ClinVar for clinical significance, and dbSNP for common variants, to prioritize novel or
clinically relevant findings.
· AI-Augmented Analysis: Intelligent Insights
What truly sets Alstronix apart is
our integration of proprietary AI tools into the analysis workflow. These
advanced machine learning modules are designed to:
o
Prioritize Clinically Relevant
Variants: Our AI algorithms learn from vast datasets to
identify and rank variants based on their likelihood of being causative for a
disease, significantly reducing the manual review burden.
o
Flag Potential Disease Associations: Beyond known associations, our AI can identify novel or subtle patterns
in genetic data that may suggest a link to particular disease phenotypes,
accelerating discovery and improving diagnostic yield. This AI layer transforms
raw genomic data into actionable intelligence, making the interpretation
process more efficient and insightful.
Pipeline Overview: From Sample to Insight
Our rWGS workflow is a robust,
multi-step process ensuring precision and reliability:
1.
Sample Input & Sequencing: High-quality DNA samples are carefully processed and subjected to
Next-Generation Sequencing (NGS) platforms, typically targeting a minimum of 30x Whole Genome Sequencing (WGS) coverage. This depth
ensures sufficient reads for accurate variant calling across the entire genome.
2.
Quality Control: Initial raw sequencing data undergo rigorous QC using FastQC and MultiQC to assess data
quality, identify potential issues, and generate comprehensive reports.
Low-quality reads and adapter sequences are then trimmed using Trimmomatic and Cutadapt.
3.
Alignment & Sorting: Cleaned reads are precisely aligned to the latest human reference
genome (GRCh38) using BWA. The resulting
alignment files (BAM) are then sorted and indexed using SAMtools
for efficient downstream processing.
4.
Duplicate Marking: PCR duplicates, which can arise during library preparation, are
identified and marked using Picard Tools to ensure
that variant calls are based on unique molecular evidence, preventing false
positives.
5.
Variant Calling: This crucial step identifies genetic variations. We employ either GATK HaplotypeCaller or DeepVariant, depending
on the specific characteristics of the data and the desired
sensitivity/specificity, to accurately detect both SNPs and Indels.
6.
Annotation & Filtration: Raw variant calls are then extensively annotated using VEP and ANNOVAR to provide
functional context (e.g., gene, exonic/intronic, effect on protein). Variants
are subsequently filtered against comprehensive public databases like gnomAD, ClinVar, and dbSNP to prioritize rare, clinically significant, or novel
variations.
7.
AI-based Prioritization: Our proprietary machine learning modules come into play here, analyzing
the filtered and annotated variants. They prioritize those most likely to be
disease-relevant, highlight potential clinical associations, and offer a ranked
list for focused interpretation.
8.
Report Generation: The final output is a clear, concise, and actionable summary report.
This includes a detailed classification of identified variants, along with
actionable insights that can guide clinical decisions or research directions.
Use Cases: Broadening the Impact of Genomics
The versatility and robustness of
Alstronix Technologies' rWGS solution make it invaluable across a wide spectrum
of applications:
· Hospitals
& Diagnostics: Our rapid turnaround time and high
accuracy are critical for the accelerated diagnosis of rare genetic diseases,
often ending prolonged diagnostic odysseys for patients and families. Early and
precise diagnosis enables timely interventions and personalized management.
· Clinical
Research: rWGS is a foundational tool for designing and
executing sophisticated clinical research studies, including large-scale
case-control studies to identify disease-associated genes, and cohort-based genome
studies to track genetic influences on health outcomes over time.
· Population
Genetics: For researchers exploring human genetic diversity,
our rWGS, optimized for Indian populations, is ideal for comparative studies
across regional ancestries, tracing migration patterns, and understanding the
genetic basis of population-specific traits or disease susceptibilities.
· Pharmaceutical
R&D: In the era of precision medicine, genomic stratification is vital.
Pharmaceutical companies can leverage our rWGS to identify patient subgroups
most likely to respond to specific therapies, improve drug target
identification, and design more effective and safer clinical trials.
Deliverables: Comprehensive and Actionable Outputs
Upon completion of the rWGS analysis,
Alstronix Technologies provides a suite of comprehensive deliverables:
· Annotated
VCF & Variant Summary Report: The Variant Call
Format (VCF) file contains all identified variants with detailed genomic
coordinates and genotypes, while the accompanying summary report provides a
user-friendly overview of key findings, including variant classification (e.g.,
pathogenic, likely pathogenic, VUS - Variant of Uncertain Significance).
· Quality
Metrics Report: A thorough report detailing the
quality of the sequencing data, including FastQC outputs, alignment statistics
(e.g., mapping rate, coverage depth uniformity), and duplication rates,
ensuring full transparency and confidence in the data.
· Custom
Visualizations (on request): For specific research or
presentation needs, we offer the generation of custom visualizations, such as
genomic coverage plots, variant allele frequency graphs, or ideograms
highlighting regions of interest.
· Optional
Clinical Interpretation Layer (AI-powered): For diagnostic
applications, we offer an additional, AI-powered clinical interpretation layer.
This advanced service integrates patient phenotype information with the genomic
data, leveraging our AI algorithms to provide a more refined and actionable
clinical interpretation of the identified variants, guiding diagnosis and
treatment strategies.
