Tuesday, August 12, 2025

Introduction to Spatial Transcripomics by Oleksandra Karpiuk

 from https://www.linkedin.com/pulse/introduction-spatial-transcripomics-ncctuebingen-w47oe/

Spatial transcriptomics is a rapidly emerging field that integrates gene expression profiling with spatial context within tissues, enabling unprecedented insights into cellular organization and function. Unlike bulk or single-cell RNA sequencing, which dissociate cells from their native microenvironment, spatial transcriptomics preserves the architectural integrity of tissues while capturing transcriptional activity. The conceptual foundation of spatially resolved transcriptomics was established in the late 2000s, with early techniques relying on in situ hybridization and laser capture microdissection. A significant milestone was achieved in 2016 when high-throughput spatial barcoding methods were introduced, notably by Ståhl et al., laying the groundwork for scalable, genome-wide spatial analysis. Subsequent technological advancements, such as Slide-seq, MERFISH, and 10x Genomics’ Visium platform, have improved resolution, throughput, and ease of use. These innovations have broadened the applicability of spatial transcriptomics across developmental biology, oncology, and neuroscience. As the field matures, the integration with multi-omics and spatial proteomics is poised to further enhance our understanding of tissue heterogeneity and pathology. The promise of spatial transcriptomics lies not only in its technical capabilities but also in its potential to transform clinical diagnostics and personalized medicine.

Spatial vs. Single-Cell Sequencing: Advantages

  • Preservation of spatial context: Spatial transcriptomics retains the native architecture of the tissue, allowing researchers to link gene expression patterns to precise anatomical locations—information that is lost during the dissociation process required for scRNA-seq.
  • Reduction of dissociation bias: Because it avoids enzymatic or mechanical dissociation, spatial transcriptomics minimizes cell-type specific biases that can arise from differential lysis or stress responses, which can distort the transcriptional profile in scRNA-seq.
  • Improved resolution of rare cell types and transitional states: By preserving spatial proximity, spatial transcriptomics can capture rare or transient cellular phenotypes that may be lost or underrepresented in pooled single-cell suspensions.
  • Integrated pathology and molecular data: Spatial transcriptomics can be directly applied to histological tissue sections, facilitating integrative analyses that align morphological features with transcriptomic signatures—critical for applications in clinical pathology and diagnostics.
  • Lower sample preparation complexity for archived tissues: Certain spatial protocols can be adapted to work with formalin-fixed, paraffin-embedded (FFPE) samples, which are commonly used in clinical settings, whereas scRNA-seq requires fresh or cryopreserved cells.

Bottlenecks and Limitations

  • Lower transcriptome coverage: Many spatial transcriptomics platforms capture only a subset of the transcriptome, especially compared to scRNA-seq, limiting detection of low-abundance transcripts.
  • Limited spatial resolution: Not all platforms can achieve single-cell or subcellular resolution, particularly in dense tissues, which can hinder accurate cell-level mapping.
  • High cost and resource demands: The equipment, reagents, and data infrastructure needed are costly, potentially restricting access for smaller facilities or projects with budget constraints. Moreover, spatial transcriptomics often incurs higher per-sample costs than scRNA-seq due to proprietary slides, imaging demands, and data processing.
  • Complex data analysis and interpretation: Data analysis requires advanced bioinformatic expertise, with workflows that are still in development and often lack standardization.
  • Tissue-dependent variability: Performance can vary widely across tissue types due to differences in sectioning quality, RNA integrity, and autofluorescence, impacting reproducibility.
  • Scalability and throughput limitations: Most spatial methods are less scalable than droplet-based single-cell approaches, limiting feasibility for large cohort studies.

Here is a simplified comparison highlighting key differences between spatial, scRNA-seq and bulk RNAseq:

Article content

Spatial transcriptomics has emerged as a powerful tool bridging the gap between histology and transcriptomics. While it presents distinct advantages in preserving spatial context and revealing cell–cell interactions within native tissue architecture, current limitations such as cost, resolution, and analytical complexity should not be overlooked. When combined thoughtfully with complementary techniques like single-cell and bulk RNA sequencing, spatial approaches hold immense potential for decoding tissue biology and advancing translational research.

References

Ståhl, P. L., Salmén, F., Vickovic, S., Lundmark, A., Navarro, J. F., Magnusson, J., Giacomello, S., Asp, M., Westholm, J. O., Huss, M., Mollbrink, A., Linnarsson, S., Codeluppi, S., Borg, Å., Pontén, F., Costea, P. I., Sahlén, P., Mulder, J., Bergmann, O., Lundeberg, J., & Frisén, J. (2016). Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science, 353(6294), 78–82. https://doi.org/10.1126/science.aaf2403

Wednesday, June 11, 2025

คุณสมบัติการจ้างงานสายวิชาการ เขาไม่ได้เลือกคนเก่ง เขาเลือกคนแก้ปัญหาให้ได้

จาก https://www.linkedin.com/feed/update/activity:7338149470498365442/?midToken=AQGaQcc-un160A&midSig=0-JfC7gpk9YrM1&trk=eml-email_notification_digest_01-hero_notification_cta-0-SHARED_BY_YOUR_NETWORK&trkEmail=eml-email_notification_digest_01-hero_notification_cta-0-SHARED_BY_YOUR_NETWORK-null-lta3ko~mbqvk6xy~uf-null-null&eid=lta3ko-mbqvk6xy-uf&otpToken=MTMwNjFmZTgxYjI4YzBjM2IxMmMwZmViNDExYWVlYjE4N2NmZDM0NzllYTc4NjZiN2JjNjA0NjY0OTU5NWZmYWYxZDdkMWU5NTdkMmZlZDk1MWYzZmM5ODAwZjA5ZTZjODZjNjhlZWE5NzM5Nzk1ODZjMjhmZTA2LDEsMQ%3D%3D


The brutal truth about academic hiring:

Committees don't hire the best researcher.
They hire the best future colleague.
The person who solves their problems.
The teammate they want to see every day.

-------------------------------------------------

75 Seconds to Decide YOUR Academic Fate.

Shocking but true.

Hiring committees spend less time reviewing your application than brewing coffee.

Here's what breaks my heart:
Brilliant PhDs obsess over publications for months.
Committees ignore them.

This explains the nightmare:
Amazing researchers with perfect CVs get rejected.
Average candidates with balanced applications get hired.
The system seems broken.
But it's not broken.
You just don't understand the rules.

Picture this committee meeting:
Your application hits the table.
Professor Smith grabs your CV.
Thirty seconds of scanning.
Done.

Your five years of PhD work.
Judged in seventy-five seconds.
Career over before it started.

But here's the secret:
The game has rules.
Most people just play it wrong.
Smart candidates learn the real scoring system.

After sitting on 25+ hiring committees, I discovered the truth.
Committees don't evaluate what you think they do.
They use 5 hidden metrics most candidates never consider.

The 5 decision-makers that actually matter:

Collaboration Potential
Question: Will you survive our faculty meetings?
Reality: Can you handle Prof Johnson who argues about everything?
Your ability to work with difficult colleagues matters.

Teaching Flexibility
Question: Will you teach Statistics at 8 AM on Fridays?
Reality: Are you willing to cover courses nobody wants?
Your adaptability trumps your expertise every time.

Departmental Gap-Filling
Question: Do you solve our immediate problems?
Reality: Are you the missing piece in our program puzzle?
Meeting their specific needs beats having the best publications.

Grant Trajectory
Question: Will you bring future funding to our department?
Reality: Can you sustain research beyond your current postdoc money?
Your potential for future grants outweighs past successes.

Personality Sustainability
Question: Can we work with you for ten years?
Reality: Will you fit our departmental culture and politics?
Being likeable determines your career longevity.

Dr. Kim learned this lesson the hard way.
Twenty-five publications.
Perfect citation record.
Zero job offers.
She was optimizing for the wrong game.

We completely rebuilt her strategy.
Stopped focusing on research output.
Started emphasizing departmental fit.
Demonstrated teaching enthusiasm.
Highlighted collaboration skills.

Next hiring cycle results:
Same qualifications.
Different strategy.
Three job offers.

The brutal truth about academic hiring:
Committees don't hire the best researcher.
They hire the best future colleague.
The person who solves their problems.
The teammate they want to see every day.

Most candidates think like job seekers.
Successful ones think like hiring committees.

Which hidden metric surprised you most?