Project #95  ·  Now Open  ·  NGS + Publication Track

Trajectory- and Cell-Type–Resolved Transcriptomic Profiling of Neuropsychiatric Symptoms in Alzheimer’s Disease

A Sex- and APOE-Stratified Precision Psychiatry Study — a six-month, clinically oriented NGS research project by BDG Lifesciences, built to end in a publication-ready manuscript.

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95
Project Number
88+
Projects Published
15+
Years of Excellence
150+
Director Publications
The Clinical Imperative
Why Neuropsychiatric Symptoms in Alzheimer’s Matter

Alzheimer’s disease is not only memory loss. Depression, anxiety, apathy, agitation, delusions and hallucinations shape caregiver burden, institutionalisation risk and quality of life — yet standard case-control transcriptomic studies cannot explain why patients with comparable pathology present so differently. This project treats those symptoms as quantitative biological traits.

Project Design at a Glance
Structured components of the six-month research plan
Brain Cell Populations Resolved
Bulk RNA-seq signals mapped to single-nucleus cell types
Project Details
What You Will Do
1
Data Acquisition, Governance & Reproducible Setup
Complete data-access applications, build a clinical metadata dictionary and sample-level audit trail, set up a version-controlled R/Python environment, and fix inclusion, exclusion and missing-data rules before any analysis begins.
2
Raw NGS Processing & Quality Control
FASTQ quality assessment, trimming, alignment or transcript-level quantification and gene-level summarisation using FastQC, MultiQC, fastp, STAR, Salmon and featureCounts inside a reproducible Snakemake or Nextflow workflow.
3
Bulk RNA-seq Statistical Analysis
Domain-specific differential expression for affective symptoms, apathy, agitation and psychosis using DESeq2, edgeR or limma-voom, adjusted for neuropathology, technical covariates and estimated cell composition, with false-discovery-rate control.
4
Sex & APOE ε4 Interaction Analysis
Test whether molecular associations with each symptom domain differ by biological sex or APOE ε4 carriage — reporting stratified estimates only where sample size and model stability are adequate.
5
Cell-Composition Deconvolution & Cellular Mapping
Estimate the contribution of excitatory and inhibitory neurons, microglia, astrocytes, oligodendrocytes and endothelial cells to determine whether signals reflect altered abundance, altered regulation, or both.
6
Network Biology & Single-Nucleus Validation
WGCNA co-expression modules, Gene Ontology and Reactome enrichment, STRING/Cytoscape network mapping, and donor-level pseudobulk validation across SEA-AD, ssREAD and independent GEO single-nucleus datasets.
7
Explainable Machine Learning & Translational Prioritisation
Nested cross-validation with elastic-net, random forest, SVM and XGBoost, SHAP-based interpretation, a compact 10–30 gene panel, and drug-target mapping through DGIdb, Open Targets, DrugCentral and ChEMBL.

Click any row to expand domain details.

DomainRepresentative ManifestationsKey MetricsScope
AffectiveDepression, anxiety, dysphoria, emotional distressMean / max severity, persistence, cumulative burdenCore
Affective symptoms — depression, anxiety, dysphoria and emotional distress — are modelled as quantitative traits: mean severity, maximum severity, persistence across consecutive assessments and time-weighted cumulative burden, rather than a single yes/no label.
ApathyReduced motivation, reduced initiative, emotional indifferencePersistent apathy, longitudinal slope, high vs low burdenCore
Apathy is captured through persistence across visits, the rate of worsening or improvement, and high-burden versus low-burden classification — allowing molecular programmes to be linked to how apathy actually unfolds over time.
AgitationIrritability, aggression, restlessness, disinhibitionEpisode frequency, severity trajectory, cumulative burdenCore
Agitation — irritability, aggression, restlessness and disinhibition — is characterised by episode frequency, severity trajectory and cumulative burden, so that patients with comparable neuropathology but very different behavioural courses can be compared directly.
PsychosisDelusions, hallucinations, paranoid ideationPresence, persistence, onset timing, severityCore
Psychosis — delusions, hallucinations and paranoid ideation — is modelled through presence, persistence, onset timing and severity. A psychosis-positive versus psychosis-negative contrast is one candidate outcome for the explainable prediction module.
Sleep (optional)Circadian disruption, nocturnal behaviour, sleep disturbanceRepeated sleep-related symptom burdenOptional
Sleep-related disturbance is included as an optional domain, subject to cohort availability and the quality of repeated sleep-symptom measurements.
DeliverableDescriptionValue
Curated Clinical–Expression DatasetHarmonised symptom, demographic, pathology and gene-expression data✓ Transparent analysis
NGS Analysis PipelineDocumented QC, quantification and statistical workflow✓ Portfolio-ready competency
Domain-Specific SignaturesGene lists for affective symptoms, apathy, agitation and psychosis✓ Mechanistic differentiation
Shared BPSD SignatureCross-domain molecular programme✓ Common therapeutic biology
Sex/APOE-Stratified FindingsInteraction estimates and subgroup-specific results✓ Precision psychiatry
Cell-Type MapNeural and glial localisation of candidate signals✓ Biological interpretability
Co-expression & Regulatory NetworksModules, hubs and enriched pathways✓ Systems-level insight
Predictive Gene PanelCompact and explainable candidate signature✓ Biomarker hypothesis
Translational Target MapPrioritised pathways, proteins and drug-target relationships✓ Future therapeutics
Manuscript PackageAbstract, figures, tables, methods, results framework and references✓ Publication & conferences
Training DossierCode repository, data dictionary, presentation and technical report✓ Academic & career development
Core Analytical Layer — Included in This Project
Sex- and APOE ε4-Stratified Precision Psychiatry

Biological sex and APOE ε4 genotype can modify both Alzheimer’s disease progression and psychiatric manifestation, yet these interactions are rarely built into symptom-focused transcriptomic models. This module adds interaction models — symptom burden × sex, symptom burden × APOE ε4 status and symptom burden × neuropathological severity — to the core pipeline, with cautious reporting wherever subgroup sample sizes are limited.

Participants completing it learn to convert psychiatric observations into measurable phenotypes, evaluate confounding, and communicate clinically restrained conclusions.

Discovery & Validation Resources
ResourceRole in the ProjectStage
ROSMAP / AMP-ADPrincipal discovery resource — longitudinal clinical evaluation, behavioural assessment, postmortem neuropathology, genotype and RNA-seq✓ Discovery
SEA-ADSingle-nucleus and spatially resolved validation across the Alzheimer’s disease pathological spectrum✓ Validation
ssREADCurated discovery and comparison of Alzheimer’s-related single-cell, single-nucleus and spatial datasets✓ Validation
GSE174367Large prefrontal-cortex single-nucleus multi-omic dataset for cell-type and disease-stage validation✓ Validation
GSE138852Entorhinal-cortex single-nucleus dataset for independent regional validation✓ Validation
MIT ROSMAP single-nucleusOptional matched or related single-nucleus validation within ROSMAP-derived samples, subject to access✓ Optional
What You Gain
Skills & Competencies Built

The project is deliberately designed to develop both computational capability and clinical reasoning — you will not merely operate software, you will learn to frame, model and defend a clinically meaningful question.

⬡
Clinical & Psychiatric Reasoning
Turning behavioural observations into measurable, longitudinal psychiatric phenotypes and interpreting symptom heterogeneity
⬡
NGS & Bioinformatics
FASTQ quality control, alignment, quantification, count matrices and reproducible Snakemake / Nextflow workflows
⬡
Biostatistics
Differential expression, interaction modelling, longitudinal metrics, FDR correction and sensitivity analysis
⬡
Single-Cell Genomics
Cell annotation, donor-level pseudobulk analysis, cell-type-specific validation and batch-aware integration
⬡
Systems Biology
Co-expression networks, pathway analysis, regulatory networks and protein-interaction mapping
⬡
Machine Learning
Parsimonious modelling, nested validation, calibration and SHAP-based explainability
⬡
Scientific Communication
Protocol writing, manuscript preparation, figure design, oral presentation and critical discussion
⬡
Research Governance
Data-use compliance, privacy, documentation and reproducible research practice
Who Should Join
Is This Project For You?

Designed for a medicine-oriented student pursuing future training in psychiatry, and equally valuable for anyone who wants a rigorous, publication-oriented neurogenomics project. The analytical tools and methods are introduced as part of the project.

Medical Students
MBBS / MD / pre-medical students who want to combine clinical reasoning with genomic research before applying for training
Future Psychiatry Trainees
Students and early-career clinicians aiming for psychiatry, geriatric psychiatry or neurology who want computational research credentials
Neuroscience & Life Science Graduates
BSc / MSc graduates seeking applied NGS and transcriptomics experience for their CV and portfolio
PhD Applicants
Candidates building competitive SOP statements and publishable research credentials for international programmes
Clinical Researchers
Clinicians and clinical scientists wanting hands-on skills in transcriptomics, biostatistics and single-nucleus analysis
Bioinformatics & Data Professionals
Analysts moving into neurogenomics who want a complete, publication-oriented project on real brain datasets
Fees & Payment Plan
Flexible 3-Stage Payment — NGS + Publication Track

The total program fee is split across three instalments so each payment is tied to tangible research progress. All payments are made in Australian Dollars (AUD) through Stripe.

Total program fee
$1,750 (AUD)
approx. $1,200 (USD)
Track
NGS + Publication
6-month research project
Duration
6 months
3 payment stages
Payment method
Stripe
Charged in AUD
Payment distribution
Stage 1
A$590
34% · at registration
Stage 2
A$590
34% · after 2 months
Stage 3
A$570
32% · after 5 months
Month-by-month view
Month 1
Protocol & Data
A$590 due
Month 2
RNA-seq QC
—
Month 3
Association
A$590 due
Month 4
Cells & Networks
—
Month 5
Validation
—
Month 6
Manuscript
A$570 due
Stage 1 window
Stage 2 window
Stage 3 window
Stage-by-stage breakdown — click to expand
1
Stage 1 — Protocol, Data Access & RNA-seq QC A$590 34% Expand ⌄
Due at registration · Covers months 1–2
Literature ReviewData AccessPhenotype FrameworkBulk RNA-seq QC
  • Welcome kit — software setup guide, reading list and data-access guidance for ROSMAP / AMP-AD
  • Month 1 — literature review, data-access applications, neuropsychiatric phenotype framework, metadata dictionary and reproducible environment
  • Month 2 — bulk RNA-seq quality control, count-matrix preparation, exploratory analysis, sample exclusions, covariate and batch assessment
  • Milestones — approved protocol with harmonised metadata schema, and an analysis-ready discovery dataset
  • Stage-gate reviews at the end of Month 1 (data access and feasibility) and Month 2 (covariates and exclusion criteria)
  • Weekly 1:1 Zoom sessions with assigned mentor, with session recordings provided
  • Access to a dedicated project support group
Why A$590 at this stage? The first payment secures your seat and activates onboarding — data-access support, protocol design, the metadata schema and the reproducible analysis environment. This groundwork happens before any statistics are run, and it is what makes the later analysis defensible. Stage 1 is non-refundable once onboarding has commenced.
2
Stage 2 — Association, Interaction & Cellular Validation A$590 34% Expand ⌄
Due after 2 months (start of month 3) · Covers months 3–5
Differential ExpressionSex / APOE InteractionsDeconvolutionSingle-Nucleus Validation
  • Month 3 — domain-specific differential expression, longitudinal symptom modelling, and sex and APOE ε4 interaction analyses
  • Month 4 — cell-composition deconvolution, pathway enrichment, co-expression and regulatory-network analysis
  • Month 5 — single-nucleus RNA-seq processing, donor-level pseudobulk analysis and cell-type-specific validation
  • Milestones — primary molecular association results, a biological-module and cell-composition map, and an independent cellular validation package
  • Stage-gate reviews at the end of Month 3 (select credible symptom domains) and Month 5 (confirm which genes and modules pass validation)
  • Weekly 1:1 Zoom sessions with mentor
  • Mid-project scientific review and written feedback from guide
Why A$590 at this stage? By month 3 you hold an analysis-ready dataset and an approved protocol — tangible evidence of progress. This payment covers the scientific core of the project: three months of interaction modelling, cell deconvolution, network analysis and single-nucleus validation, where most of the mentor’s review time is spent.
3
Stage 3 — Prediction, Translation & Manuscript Delivery A$570 32% Expand ⌄
Due after 5 months (start of month 6) · Covers month 6
Explainable MLDruggabilityManuscriptReproducibility Archive
  • Month 6 — explainable prediction, druggability analysis, and final figures and tables
  • Manuscript, presentation and repository documentation — a submission-ready research package
  • Final stage-gate: freeze the analysis, manuscript figures and reproducibility archive
  • Training dossier — code repository, data dictionary, presentation and technical report
  • Official BDG Lifesciences certificate of completion
  • Personalised letter of recommendation from your guide
  • Weekly 1:1 Zoom sessions with mentor through to manuscript submission
Why A$570 — the final stage — at this point? By the end of month 5 you have validated results and a clear picture of the scientific and professional value built. The final, slightly lower payment carries you through prediction, translational mapping and manuscript preparation, and releases the career-defining deliverables: the manuscript package, certificate and letter of recommendation.
Payment summary
StageWhen to PayAmount (AUD)% of TotalUnlocks
Stage 1
At registrationA$59034%Onboarding, protocol, data access, RNA-seq QC
Stage 2
After 2 monthsA$59034%Association, interaction and single-nucleus validation
Stage 3
After 5 monthsA$57032%Prediction, manuscript, certificate, recommendation
TotalOver 6 monthsA$1,750100%Complete NGS + Publication research project
Payment terms: The total fee is A$1,750 (approx. US$1,200) and all payments are made in Australian Dollars (AUD) through Stripe. Stage 1 (A$590) is non-refundable once onboarding has commenced. Stage 2 (A$590) is due after 2 months for participants in good standing. Stage 3 (A$570) is due after 5 months and releases the manuscript package, certificate and letter of recommendation. All fees are non-transferable. Full details are in the Terms & Conditions below. For queries, contact research@bdglifesciences.com
Terms & Conditions
  1. Fees & currency. The total program fee is A$1,750 (Australian Dollars), indicatively equivalent to US$1,200. All payments are charged in Australian Dollars (AUD) and processed through Stripe. The US dollar equivalent is shown for reference only; your bank or card issuer may apply its own exchange rate and fees.
  2. Instalments. Stage 1: A$590 at registration. Stage 2: A$590, due after 2 months of the project (start of month 3). Stage 3: A$570, due after 5 months of the project (start of month 6). Stage 2 is due for participants in good standing.
  3. Secure checkout. Payments are made through Stripe’s secure checkout. Card details are handled by Stripe and are not stored by BDG Lifesciences.
  4. Refunds & transfers. Stage 1 is non-refundable once onboarding has commenced, as it covers data-access support, protocol design, software setup and mentor allocation. All fees are non-transferable.
  5. Stage 3 deliverables. Manuscript finalisation, certificate issuance and the letter of recommendation are released upon confirmation of Stage 3 payment.
  6. Data access. Some datasets (e.g. ROSMAP symptom-level variables) are controlled-access and depend on approval by the data custodians. Participants must comply with all data-use agreements, must not attempt re-identification, and must not export restricted individual-level information.
  7. Research outcomes. BDG Lifesciences supports manuscript preparation, but no journal acceptance can be guaranteed. Findings are research findings, not clinical diagnostic tests.
  8. Queries. Contact research@bdglifesciences.com before making payment if you have any questions about these terms.
Common Questions
Frequently Asked Questions
Rather than a conventional Alzheimer’s-versus-control comparison, the project asks why patients with comparable neurodegenerative pathology develop different psychiatric and behavioural manifestations — depression, apathy, agitation, psychosis and, optionally, sleep disturbance — and which brain-cell-specific transcriptional programmes are associated with them, including how sex and APOE ε4 status modify these programmes.
It is a real, retrospective, computational research project. You work with clinically phenotyped bulk RNA-seq and independent single-nucleus datasets, follow a pre-specified analysis plan with stage-gate reviews, and finish with a submission-ready research package including a manuscript framework, figures and a reproducible code repository.
The principal discovery resource is ROSMAP (via the AMP-AD / AD Knowledge Portal), with SEA-AD, ssREAD and GEO datasets GSE174367 and GSE138852 used for single-nucleus validation. ROSMAP symptom-level variables are controlled-access, so data-access applications are submitted in Month 1 and a secondary public-dataset plan is maintained in case of delay.
The project is designed for a medicine-oriented student pursuing future training in psychiatry, and that clinical framing runs through it. Life science, neuroscience and bioinformatics graduates and professionals are equally welcome; a background in medicine or life sciences is helpful, and the analytical tools and methods are introduced as part of the project.
FastQC, MultiQC, fastp, STAR, Salmon, featureCounts, DESeq2 / edgeR / limma-voom, sva or RUVSeq, WGCNA, STRING and Cytoscape, plus R and Python with Snakemake or Nextflow for reproducible workflows. Machine-learning and translational modules use elastic-net, random forest, SVM, XGBoost, SHAP, DGIdb, Open Targets, DrugCentral and ChEMBL.
The project is built around a defensible publication pathway: longitudinal symptom phenotyping, bulk RNA-seq association analysis, sex/APOE effect modification and independent cell-type validation. No journal acceptance can be guaranteed — publication strength depends on access to adequately phenotyped data and rigorous independent validation.
The total fee is A$1,750 (approximately US$1,200), paid in three instalments — A$590 at registration, A$590 after 2 months and A$570 after 5 months. All payments are made in Australian Dollars (AUD) through Stripe. The US dollar figure is indicative only; see the Terms & Conditions in the payment section.
Payments are processed in AUD on Stripe. If your card or bank account is in another currency, your card issuer converts the amount at its own rate and may charge conversion fees, which are outside BDG Lifesciences’ control.
It uses retrospective postmortem data, so results are research findings rather than clinical diagnostic tests, and computational drug-target mapping does not imply therapeutic efficacy. Sex- and APOE-stratified estimates are reported only where sample sizes allow, and the project plan documents each limitation with a mitigation strategy.
Unlike generic internship programmes, Project #95 is built around a defined, unsolved research question with a stage-gated plan and a publication outcome. With 88+ internationally published projects and 15+ years of experience, BDG Lifesciences delivers scientific credibility backed by a proven track record.

Secure Your Place in Project #95

Seats are strictly limited to maintain mentorship quality. Register now to begin your research journey — Stage 1 (A$590) starts upon registration. Payments are processed securely in Australian Dollars via Stripe.

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