Course info

Objective: To master and implement advanced statistical frameworks for the analysis of large-scale retinal recordings. The student will apply these methods to investigate how the absence of microglia during mouse retinal development alters retinal population activity, with a focus on:
Spectral Analysis: Determining if microglia-deficient retinal ganglion cells (RGCs) lose their ability to "phase-lock" to stimulus frequencies or if their preferred frequency tuning shifts.
Unsupervised Clustering: Quantitatively defining functional cell types based on their stimulus-response profiles to categorize developmental deviations due to microglia-deficienncy.

Session 0: Defining learning goals
Discuss the aim of the course; the experiment, the scientific question, and the data to be analyzed (we already did this yesterday).

Session 1: Fourier Analysis of Neural Firing
Theory: Stationary signal processing, the Wiener-Khinchin theorem, and power spectral density (PSD) estimation.
Assignment: analyzing dominant rhythms in retinal recodings.
Recommended Material:
Veritasium: https://www.youtube.com/watch?v=nmgFG7PUHfo&t=1460s; https://www.youtube.com/watch?v=IgF3OX8nT0w
3Blue1Brown: https://www.youtube.com/watch?v=spUNpyF58BY&t=19s
Mike X Cohen: https://www.youtube.com/watch?v=v743U7gvLq0&list=PLn0OLiymPak28kNU6D_nkUBebb5LRj3E5&index=8

Session 2: Time-Resolved Frequency Analysis (Wavelets)
Theory: The uncertainty principle in signal processing; Morlet Wavelets vs. Short-Time Fourier Transform (STFT).
Assignment: Generating spectrograms to see how the frequency of retinal responses evolves from the onset of the stimulus.
Recommended Material:
3Blue1Brown: https://www.youtube.com/watch?v=MBnnXbOM5S4&t=174s
Mike X Cohen: https://www.youtube.com/watch?v=T9x2rvdhaIE

Session 3: Phase Dynamics and the Hilbert Transform
Theory: Analytic signals, instantaneous phase, and envelope extraction.
Application: Analyzing phase-locking and synchrony. Do cells in the deficient retina still fire at the same "part" of the stimulus cycle as controls?
Recommended Material:
Mike X Cohen: https://www.youtube.com/watch?v=VyLU8hlhI-I ; https://www.youtube.com/watch?v=jy7IxIXUAJk ; https://www.youtube.com/watch?v=6x3iFs_j5j8

Session 4. Dimensionality Reduction:
Theory: PCA, UMAP
Assignment: Apply dimensionality reduction to the response features of recorded retinal neurons.
Recommended Material:
Statquest:
https://www.youtube.com/watch?v=FgakZw6K1QQ&pp=ygUNcGNhIGV4cGxhaW5lZA%3D%3D
youtube.com/watch?v=eN0wFzBA4Sc&t=67s&pp=ygUOVU1BUCBleHBsYWluZWQ%3D

Session 5. Clustering & Supervised classification
Theory: K-Means clustering, hierarchical clustering, HDBSCAN, logistic regression
Assignment: Cluster neurons in the reduced feature space. Fit logistic regression to microglia vs control labels.
Recommended Material:
Statquest:
https://www.youtube.com/watch?v=4b5d3muPQmA
https://www.youtube.com/watch?v=7xHsRkOdVwo
https://www.youtube.com/watch?v=RDZUdRSDOok
youtube.com/watch?v=yIYKR4sgzI8&pp=ygUTbG9naXN0aWMgcmVncmVzc2lvbg%3D%3D

Session 6. Statistical validation and interpretation
Theory: Cross-validation, Bootstrapping
Assignment: Examine significance of clustering and classification results with statistical analyses.
Recommended Material:
Statquest
youtube.com/watch?v=Xz0x-8-cgaQ&pp=ygUXYm9vdHN0cmFwcGluZyBzdGF0cXVlc3Q%3D
https://www.youtube.com/watch?v=fSytzGwwBVw

Target group: This is a mentored self-study course for Natalie Gutmann-Oezge

Prerequisites: None

Evaluation: Course requirements include regular technical assignments focused on the implementation of advanced statistical methods using the student's primary dataset. Each session, we discuss the student's presentations of the results, focusing on both technical accuracy and the interpretation of the results.

Teaching format: Mentored study

ECTS: 1 Year: 2025

Track segment(s):
Elective

Teacher(s):
Luka Gantar Gabor Lengyel

Teaching assistant(s):