Pipi three-data-centre model revisited

Mike's Notes

I was greatly influenced by a recent article by Gennaro Cuofano in The Business Engineer about how Apple ensures Privacy.

Gennaro wrote ..."

Apple’s response is not to win training. It is to dominate inference

Apple’s strategy is internally coherent:

Tier 1: On-device inference

    • Small local models handle personal and contextual tasks.
    • These run without network dependency and with minimal privacy leakage.

Tier 2: Private Cloud Compute

    • Apple Silicon-based servers handle workloads beyond device capacity.
    • The architecture is stateless and privacy-preserving.

Tier 3: Third-party frontier models

    • Apple relies on external model providers such as Google and OpenAI for world knowledge and advanced reasoning.
    • These models are treated as backend commodities underneath Apple’s interface layer.

..."

Resources

References

  • Reference

Repository

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Last Updated

29/03/2026

Pipi three-data-centre model revisited

By: Mike Peters
On a Sandy Beach: 29/03/2026

Mike is the inventor and architect of Pipi and the founder of Ajabbi.

Data Centres

Because of its unusual architecture and the priority given to privacy and security, Pipi needs three separate data centres that work together in a chain.

Rendering > Staging > Cloud

  • Rendering: Build enterprise applications.
  • Staging: Send updates, localise and deploy enterprise applications.
  • Cloud: Hosting of enterprise applications for scaling and integration.

I like the way Apple ensures privacy for people using AI on their iPhone. Any extra AI work is offloaded to Apple's cloud servers for processing, which are stateless and store nothing. That got me thinking.

Could part of Pipi be made stateless to add extra privacy like Apple?

The way Pipi is designed;

  • Rendering: Unable to see any customer data.
  • Cloud: Unable to see any Pipi config data.
This is to be done by using separate databases hosted in separate data centres.

Possible data centre model

  • Rendering: This is stateful; each agent-engine has its own database. Each enterprise customer has a separate physical server to host a digital twin.
  • Staging
    • Inwards-server: Receive anonymised logs
    • Outwards-server: Send updates, localise and deploy enterprise applications.
  • Cloud: This would be stateful using customer-eyes-only databases.

Would that work? How?

This might only be discovered during wild ML experiments in a future startup AI Accelerator.

How RNNs Work (And Why Everyone Stopped Using Them)

Mike's Notes

A great explanation of how RNNs work.

Resources

References

  • Attention is All You Need by Ashish Vaswani, Noam Shazeer, Niki Parmar, Jakob Uszkoreit, Llion Jones, Aidan N. Gomez, Lukasz Kaiser, Illia Polosukhin. 2017. ArXiv 1706.03762.

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Last Updated

28/03/2026

How RNNs Work (And Why Everyone Stopped Using Them)

By: Dr. Ashish Bamania and Jose Parreño Garcia
Into AI: 07/02/2026

Dr. Ashish Bamania: I help you to level up in AI and Quantum Computing
Jose Parreño Garcia: I write about Data Science, Machine Learning and leading data teams. I have built teams from scratch and lead 50+ data scientists @Skyscanner. Now, I share my experience with you.

A gentle walkthrough of how Recurrent Neural Networks (RNNs) work, and the math that breaks them.

This week’s newsletter is written by Jose Parreño Garcia. He is a senior Data Science manager at Skyscanner.

He regularly shares insights on building effective teams, developing leadership skills, and advancing careers in Data Science and Machine Learning through his newsletter, Senior Data Science Lead.

You can also find him and stay up to date with his content on LinkedIn.

This week, I went all the way back to 2017. That’s when the now-legendary ‘Attention is All You Need’ paper came out — the one that introduced the world to Transformers, and set the foundation for everything from ChatGPT to image generation to code-writing copilots.

And sure, I could jump straight into explaining how Transformers work. But given the impact these models have had — and the fact that you probably see the word “attention” 30 times a week now — I thought it would be worth taking a step back (actually 2 steps back).

Before we can truly understand Transformers, we need to understand where they came from. And that means revisiting the architectures that paved the way: Recurrent Neural Networks (RNNs) and Long Short-Term Memory (LSTM) networks.

In this blog post, I am diving into RNNs.

We will walk through what they are, how they work, and most importantly, why they struggle. By the end, RNNs will feel like a clever little for-loop with memory instead of scary maths magic.

Ready? Let’s jump in!

What we will cover in this article

  1. How is an RNN different from a classical Deep Neural Network? (or other classical sequence models)
  2. Introducing a made-up use case with 3 data points for Stock price prediction
  3. The scary official diagram of an RNN cell. (Don’t worry, we will break it down super easily.)
  4. A walkthrough of RNN calculations (And you will see how the maths is not that scary after all.)
  5. Three problems associated with RNNs

How is an RNN different from a classical Deep Neural Network?

I assume in this post that you have worked with (or are familiar with) the basics of classical Deep Neural Networks (from here on, DNNs).

If my assumption is correct, then the diagram below should feel really familiar. It is a diagram of a DNN with:

  • X: A set of input nodes, representing the variables you want to use for prediction.
  • H1, H2: 2 hidden layers with 4 nodes. This is where the parameters that learn how to dial up or down specific signals from X. Basically, the knobs the model adjusts to learn.
  • Y: The prediction node. In this case, it’s only 1 for simplicity.

Diagram of a classical Deep neural network (DNN)

Now, there are 2 main things to highlight in this diagram:

  1. The DNN processes all the data at once.
    You see the X input? From a DNN’s perspective, it’s a torrent of data, all pushed and processed at once. There is nowhere in this diagram that the network can say, “Hey, can you just send me X1 and X2 first, and then I can process X3 and X4?”.
  2. The DNN is feed-forward (or sequential).
    In other words, the data flows from left to right (from X → Y). There is nowhere in this diagram that a node can stop the data flow and ask: “Hey, what data did I have in the previous step?” It is oblivious to that.

DNNs are really powerful, but they are also “memory-less”

DNNs are “memory-less” because of the two points mentioned above. And being “memory-less” means that DNNs really struggle to predict when sequence or order matters.

Take a simple stock price prediction scenario. The only way that DNNs can consider what happened yesterday or the day before is if you tell them what matters. This is usually done by manually creating features like:

  • Yesterday’s price
  • A moving average over the past 7 days
  • A sine-transformed day-of-week feature to capture seasonality

But wasn’t Deep learning supposed to eliminate Feature engineering?

Yes (and no).

Neural networks do learn internal representations (i.e., “features”) from raw data. But when it comes to sequences, classical deep neural nets still need all the help they can get (so, kind of back again to square one, where we have to feature engineer stuff…)

This is where Recurrent Neural Networks (RNNs) come in.

Recurrent neural networks (RNNs) are a class of artificial neural networks designed for processing sequential data, such as text, speech, and time series, where the order of elements is important.

Their two main characteristics are:

  1. RNNs process one input at a time.
    Instead of taking all of the input X in one big gulp, RNNs look at one data point at a time — like reading a sentence word by word, or stepping through a stock price day by day. This allows them to focus on how each input evolves over time.
  2. RNNs are recursive.
    Yes, the information flows left to right, but at each step, it can also look at what happened before (kind of a right-to-left motion). It’s like a left-to-right with memory.

Don’t worry if this feels dense right now, we will break it down step by step.

By the end of this post, you will not only understand what “recurrent connections” mean, but you will also see why RNNs became a foundational architecture for handling sequences.

Introducing a made-up use case for Stock price prediction

Ok, before we get into the RNN section, let me introduce you to the simplest stock price prediction exercise in the course of human history.

The diagram below shows a toy time series where:

  • For simplicity, all stock prices are set to 0.
  • We have 3 data points.
  • The idea is to use yesterday’s and today’s stock prices to predict tomorrow’s stock price.

I want to introduce this in such a simple way because:

  1. I want to actually show you the maths of the RNN using super simple numbers.
  2. Labelling each step as yesterday, today, and tomorrow will help anchor the RNN diagrams that follow.

Let’s keep this mental model in our back pocket — it’s going to make the scary-looking RNN diagrams feel a lot less scary.

Ok, now we are ready to get scared by a diagram of an RNN cell!

The scary official diagram of an RNN cell

So far, we have discussed how RNNs differ from classical DNNs because they remember their past. But what does that actually look like inside the model?

Well... time to face the infamous RNN diagram.

It might look like a tangle of wires and equations at first, but don’t worry, we will walk through it slowly, tie it back to the stock price example, and by the end, you will see it’s just a simple process of multiplication, addition, and a squiggly activation function or two.

The diagram below is a vanilla RNN cell.

I can sense you sweating… a flow diagram? With parameters? With maths operations? Ok, let’s break it up so that you don’t have to process it all at once.

Here are the elements to focus on:

  1. Note the X, h and Y elements (similar to the classical DNN diagram).
  2. X(t) represents today's data point, h(t-1) is what came from yesterday, h(t) is what is passed to predict tomorrow, and Y(t+1) is the predicted data point.
  3. Y(t+1) represents the prediction that we want.
  4. tanh and softmax are just activation functions. The same kind you have seen in regular neural networks, so nothing special for RNNs. They take raw values and squash them into a friendlier range, like between -1 and 1 (for tanh) or 0 and 1 (for softmax).
  5. Finally, there are a couple of blobs with mult and sum. These are just visual aids so that you can see the operations in action when we pull the numbers in.
  6. There are maths operations outside of the cell. These are basically there just so that we can transform a squashed value coming out of tanh, into a real value that makes sense. For example, transform 0.9 coming out of the tanh function to maybe $5.

✍️ Quick note

Technically, the RNN makes a prediction y(t) after seeing input x(t) and memory h(t-1).

But since in our toy example we are trying to predict the next value, it’s tempting to call it y(t+1) — just know that it’s really y(t) in the math, but the target we are aiming for is the value at t+1.

I purposely named it y(t+1) for pedagogical reasons for this post.

Let’s map this diagram with the theoretical RNN math function

In the image below, I have added the math functions that lead to the two outputs from the RNN cell: y(t+1) and h(t).

So, if we wanted to either predict an output (Y) or carry to the next stage (h), then the neural network should learn:

  • Wx: This is the weight applied to today’s data, X(t). It controls how much the model should care about today’s stock price. Extreme case, if Wx = 0, then this means we don’t care about X(t) because Wx * X(t) would yield 0.
  • Wh: This is the weight applied to the previous hidden state, h(t–1). It tells the model how much to rely on memory. If Wh = 0, the past is forgotten.
    ⚠️ Don’t misinterpret h(t-1) by thinking it is yesterday’s stock price. It is what comes out of the cell (with its multiplications, sums, and activation functions) applied to yesterday’s stock price.

  • b: This is the bias term. Think of it as a small correction applied regardless of the input. It’s important in training, but not very interesting for understanding how RNNs work conceptually (as it affects DNNs the same way). If you want to deep dive, check this link.

I believe that only when we plug in numbers to these diagrams will we start really understanding what is happening inside the RNN. Let’s do this next.

A Walkthrough With Real Numbers

Alright, time to take what we have learnt and run it step by step. Instead of just showing the internals of a single RNN cell, we’ll now “unroll” it (you will see what that is in a second).

This will finally answer the big question: how does an RNN actually use the past to predict the future?

How do we represent tomorrow’s prediction diagrammatically?

Pretty simple. We just copy and paste the same RNN cell forward in time, one per data point in our sequence.

In our toy stock price example, we only have two data points (t–1 and t), so we unroll the cell twice in order to make a prediction at t+1.

And this is why they are called recurrent, because the same logic is applied over and over, like a for loop.

Cool, now that you are comfortable with what happens inside a single RNN cell, let’s walk through this unrolled diagram in detail to ensure we are all on the same page.

  1. We begin by plugging in yesterday’s stock price. Because there is no data prior to yesterday, we can ignore the previous hidden state input h(t-2).
  2. Using both math functions, we then calculate y(t) and h(t-1). From these two, only h(t-1) is useful for us. This is the value that describes the memory, and that will be passed to the next cell. y(t) is irrelevant, so we ignore it.
  3. Finally, we plug in today’s data and run through the relevant maths operations to calculate y(t+1). You can see from the diagram that the RNN is using today’s data X(t) and yesterday’s data h(t-1) from memory to calculate what could happen tomorrow.

💡 An important highlight: Shared weights and biases

“Wait a sec... you are using the same Wx, Wh, and b in both cells. Shouldn’t they be different?”

Great question! This is the part that makes RNNs elegant, but also tricky (you will see at the end how these shared weights break an RNN’s learning process).

Unlike feedforward layers that might learn new weights for every input, an RNN cell reuses the same weights at every timestep. That’s the “recurrent” part. An RNN not only repeats the cell structure, but it also repeats the exact same function with the same learned parameters.

So yes — Wx, Wh, and b are constant across time. What changes is the input x(t) and the memory from the previous step h(t–1), which is how the model updates its thinking as it moves forward.

Plugging numbers into the diagram

Before doing some basic maths, let’s talk about the numbers being used:

  1. Note how I substituted Wh, Wx, b, W_output and b_output with numbers. I made these numbers up, but they are the ones the neural network would tweak during its learning process.
  2. The input data points are the ones we know from the time series. X(t-1) and X(t) are both 0.

Now we are ready to take pen and paper and perform all the calculations in this diagram.

Plugging in all the numbers, y(t+1) comes out to be 0. Nice, this is what we expected from our mock stock price time series!

What would the diagram look like if we had 50 data points?

Well... you would copy the RNN cell forward 49 times, just like a for loop with 50 iterations (luckily for me, I am not drawing that diagram...)

But structurally, nothing changes. You still:

  • Reuse the same weights
  • Pass memory from each time step to the next
  • And only apply the final output prediction where it matters, which is usually the last cell in the sequence

What we learn from the above examples is that:

  • RNNs reuse the same weights and biases at each step.
  • Hidden states h(t) are like memory, passed forward through time.
  • Outputs y(t) are generated by applying a linear transformation and softmax on the hidden state.
  • Even a dumb toy dataset of all zeros reveals the internal mechanics beautifully.

That wasn’t that hard, right? Well, I have bad news for you…

Three Major Problems With RNNs

These vanilla RNNs are never used for real-world use cases because they come with three big problems:

  • They are slow to train.
  • They suffer from the problem of vanishing gradients
  • They suffer from the problem of the exploding gradients

Let’s cover these in detail in their own sections.

Problem 1: Training a vanilla RNN is very slow

Deep Neural Networks (DNNs) process all their inputs at once in a single forward pass. Everything flows from left to right, layer by layer. That means training can occur in parallel across many data points and GPU cores.

This is not the case with RNNs.

Because RNNs depend on previous hidden states, they are inherently sequential. You can’t calculate h(t) until you have calculated h(t–1).

It’s like reading a book: you can’t understand chapter 5 until you have read chapter 4.

RNNs make you walk through time, one step at a time, and this sequential dependency kills parallelism.

That is the first problem: RNNs are powerful, but they pay for it in training speed.

Problem 2: The problem of the Vanishing gradients

To explain this problem, I would have to take some mathematical shortcuts. To really know what is happening under the hood, you need to be familiar with the chain rule used in backpropagation. But showing the full impact of vanishing gradients using the backpropagation formula would be overkill.

Let’s zoom in on just one parameter in the RNN, i.e. Wh, the weight that is multiplied by the previous hidden state.

In our earlier 3-step example, Wh was used once (just one multiplication). But, if you are training an RNN for 50 timesteps (say, 50 days of stock data), that means Wh shows up 49 times in the full chain of calculations.

When the model tries to update Wh via backpropagation, mathematically, the gradient is multiplying Wh over and over again, kind of like:

Uh-oh. What happens when Wh < 1?

Try plugging in Wh = 0.5:

That’s basically zero. This means that the update to Wh during training is so tiny, it’s like the model is frozen. It can’t escape its starting point. It just sits there, unable to learn anything useful.

Problem 3: The problem of the Exploding gradients

This is the opposite problem. If vanishing gradients are the slow death of learning, exploding gradients are the chaotic opposite.

What happens when Wh > 1? Say Wh = 1.5.

That’s nearly a billion. This means that during backpropagation, the gradient becomes massive. And with a gradient that large, your weight update becomes a wild jump.

The result is that your model overshoots the loss minimum, bounces around the optimisation landscape like a drunk pinball (love that game), and probably never converges.

This is the exploding gradients problem. Same root cause as vanishing gradients — compounding multiplications through time — but now the problem is too much signal, instead of too little.

What’s next: How LSTMs fixed all of this (mostly)

With everything we have covered, you might think, “Hey, that vanilla RNN was easy enough to understand, but with the stated problems, it also looks pretty useless, right?”

I would mostly agree. Training a vanilla RNN is not impossible, but it requires skill, feature engineering, fine-tuning, and time. The vanishing and exploding gradient problem is the one that mostly holds back an RNN.

This is why LSTMs were introduced.

LSTMs are improved versions of RNNs. With built-in mechanisms (called Gates) to decide what to keep, what to forget, and what to pass forward, they were designed specifically to beat vanishing and exploding gradients at their own game.

LSTMs are for the next post, where we will explore how they work and why they became the go-to tool for sequence modelling… at least until Transformers came along.

Now, I want to hear from you!

In this post, we broke down how RNNs work, from the vanilla cell structure to why they struggle to train in the real world.

We kept it simple, even used an all-zero dataset, and uncovered the quiet math that makes RNNs nearly impossible to scale.

But now I’m curious about your experience.

  • Have you ever built or trained an RNN model?
  • Did you run into vanishing gradients or the joys of exploding updates?
  • Maybe you were introduced to LSTMs (or GRUs) straight away and skipped vanilla RNNs altogether?
  • Or maybe you are just now connecting the dots between hidden states, time steps, and why Transformers were such a leap.

Drop your thoughts, experiences, or lingering questions in the comments. I would love to hear how you’ve approached sequence modelling in your ML journey.

Thanks again to Jose Parreño Garcia for writing this week’s newsletter.

Don’t forget to subscribe to his newsletter and connect with him on LinkedIn.

A roadmap for accelerators

Mike's Notes

It's getting busy, so I need a roadmap for accelerators now.

Resources

  • Resource

References

  • Reference

Repository

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Last Updated

28/03/2026

A roadmap for accelerators

By: Mike Peters
On a Sandy Beach: 27/03/2026

Mike is the inventor and architect of Pipi and the founder of Ajabbi.

Lots of opportunities are coming in.

This is a roadmap for using coaching, workshops, incubators and accelerators to develop, test and validate the Ajabbi Mission Business Model and the Pipi closed-core and Pipi open-source applications.

It is sorted by deadline. The first row of the table is a key.

Date Roadmap

deadline

Start-End

Status

Title

Description

What

To come.

  • To come

Learned

  • To come

To do/done

  • To come

Resources


deadline

2017-2020

Completed

Steve Blank

"Steve Blank (born 1953) is an American entrepreneur, educator, author and speaker. He created the customer development method that launched the lean startup movement. His work has influenced modern entrepreneurship through the creation of tools and processes for new ventures, which differ from those used in large companies."

What

Learning from the very best.

  • Reading his books and blog
  • Watching videos
  • Using all the free courses and tools

Learned

  • How to use a Business Model Canvas
  • How to use a Mission Model Canvas
  • How to do customer discovery
  • How to run experiments to validate assumptions

Done

    • Read and tried everything
    • Build Pipi Experiment Engine

    Resources

    deadline

    2020-2023

    Completed

    KiwiSaaS

    "Our community is free to join and it's where we can safely share our knowledge and experiences with each other. Paying it forward is what drives kiwiSaaS growth."

    What

    Online workshops and random monthly one-on-one meetings with other founders.

    Learned

    • To keep going
    • It is OK to make mistakes
    • Lots of insights from being open
    • Importance of listening to others

    Done

    • Get stuck in

    Resources

    January 2024

    January - October 2024

    Completed

    Startup Aotearoa

    "Startup Aotearoa ignites New Zealand’s entrepreneurial spirit by providing personalised one-to-one coaching to early-stage startup founders. Delivered nationwide through local regional providers,"

    What

    Mentoring from Mr G led to testing the ICP at Waimumu Southern Field Days 2024 on

    • Developers at Agritech companies
    • Agricultural suppliers

    Learned

    • Developers are the ICP
    • Find a teaching customer

    Done

      • Pivot ajabbi.com to developers
      • Host a teaching customer requiring 3 languages

      Resources

      April 2024

      May - November 2024

      Completed

      Creative HQ's On the Business workshop series

      "This 'On the Business' workshop series gives you the dedicated time and resource to help you grow your business. We'll provide tools, frameworks and hands-on..."

      What

      Remote workshops using Miro canvas.

      Learned

      • To come

      Done

      • To come

      Resources

      February 2025

      February 2025 - March 2025

      Completed

      NZTE Export Essentials SaaS 4-part workshop.

      "Learn what best-practise exporting involves when you sell SaaS offshore."

      What

      Workshops with individual follow-up sessions.

      Learned

      • To use the tools available to test assumptions.

      Done

      • To come

      Resources

      February 2025

      February 2025 - March 2025

      Completed

      NZTE Position for Growth workshop.

      "Our Position for Growth workshops help you define what problem you solve for"

      What

      Workshops with individual follow-up sessions.

      Learned

      • To use the tools available to test assumptions.

      Done

        • To come

        Resources

        25/03/2026

        April 2026 - March 2028

        Application Withdrawn

        Google AI Accelerator

        "With this program, you can get access to startup experts, your Google Cloud and Firebase costs covered up to $200,000 USD (up to $350,000 USD for AI startups) over 2 years, technical training, business support, and Google-wide offers."

        What

        Collaborate with DeepMind to run wild ML integration experiments to go where no developer has gone before.

        • Pipi > IaC > GCP
        • Pipi > VM > BoxLang > Workspaces
        • Pipi > MCP > DeepMind Gemini
        • Pipi > Scientific Workflows > TPU

        Learned

        • Invited to apply by a Google chap who was assisting behind the scenes using an unlisted pathway. I then discovered that free credits begin on the day of application approval, so I will reapply when ready to start in July to make the most of the 24-month window of opportunity.

        To do

        • Increase Pipi DevOps speed 1000x by completing work on the data centre, workspace rendering, and IaC to GCP free tier. This will enable fast, multiple automated experiments.

        Resources

          29/03/2026


          May-June

          Application completed

          Access Activator

          "Whaikaha, in collaboration with Creative HQ, is piloting Access Activator to find, fund and grow accessibility solutions from across New Zealand."

          What

          Test personalised accessible UI based on the GOV.UK Design System using paper mockups for

          • Autistic
          • Colour Blindness
          • Dyslexic
          • Epilepsy
          • Irlen
          • Physical & Motor Disabilities
          Involve
          • Local disabled community
          • National support organisations for Autism, Dyslexia, Muscular Dystrophy, etc

          Then, test with HTML mockups. Use experimental results to enable all Ajabbi workspace users to create a personal, accessible profile that meets their individual needs (font, colour, layout, workflow, etc.).

          Learned

          • To come

          To do

            • To come

            Resources

            31/03/2026

            April-May

            Application completed

            Creative Tech Activate

            "Designed for teams at the idea stage, this 8-week pre-accelerator programme supports founders to validate their concept, build an early prototype and/or actionable technology roadmap, connect with first customers and partners, and learn how to build a scalable business using proven startup tools."

            What

            Test screen production workspace using HTML Mockups on

            • Local Film Industry Community

            Learned

            • To come

            To do

            • To come

            Resources

            26/05/2026

            July - November 2026

            Application underway

            Sprout Accelerator

            "The Sprout Accelerator takes a cohort of agrifood innovators on a 3-month adventure to discover, articulate and refine the foundations to grow global startups."

            What

            Test farm management workspace using HTML Mockups on

            • Dairy farmer-led catchment group
            • Agritech wait list from Waimumu

            Learned

            • To come

            To do

            • To come

            Resources

            June 2026

            July 2026 - June 2028

            To apply

            Google AI Accelerator

            "With this program, you can get access to startup experts, your Google Cloud and Firebase costs covered up to $200,000 USD (up to $350,000 USD for AI startups) over 2 years, technical training, business support, and Google-wide offers."

            What

            Collaborate with DeepMind to run wild ML integration experiments to go where no developer has gone before.

            • Pipi > IaC > GCP
            • Pipi > VM > BoxLang > Workspaces
            • Pipi > MCP > DeepMind Gemini
            • Pipi > Scientific Workflows > TPU

            Learned

            • To come

            To do

            • To come

            Resources

            July 2028

            Start-End

            To apply

            Y Combinator

            "The overall goal of YC is to help startups really take off. They arrive at YC at all different stages. Some haven't even started working yet, and others have been launched for a year or more. But whatever stage a startup is at when they arrive, our goal is to help them to be in dramatically better shape 3 months later."

            What

            How a mission-driven company can solve a problem for humanity by scaling from tiny to very large.


            Learned

            • To come

            To do

            • To come

            Resources


               


               

              Continental Drift

              Mike's Notes

              This is an example of a Notebook from Observable embedded on this page using an iFrame.

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              Last Updated

              26/03/2026

              Continental Drift

              By: Nicolas Lambert
              Observable: 02/2026

              Hi. I'm Nicolas Lambert, research engineer in geographic information science at CNRS (France). My job is to draw maps and teach cartography at the university. I am a geographer 🌎, and not really a developer 🖥️.

              This notebook compresses 750 million years of continental drift in a mesmerizing animation. It includes current country boundaries, so as the animation loops, you can follow how different regions emerged over time.

              Four autism subtypes map onto distinct genes, traits

              Mike's Notes

              Note

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              Last Updated

              26/03/2026

              Four autism subtypes map onto distinct genes, traits

              By: Giorgia Guglielmi
              The Transmitter: 17/07/2025
              DOI: https://doi.org/10.53053/BZOX1294

              Giorgia Guglielmi is a freelance writer covering the life sciences, biomedicine and science policy. Her stories have appeared in Nature, Science, NOVA Next and other publications.

              Giorgia has an M.Sc. in science writing from the Massachusetts Institute of Technology and a Ph.D. in biology from the European Molecular Biology Laboratory.

              An analysis of more than 5,000 autistic children and their siblings underscores the idea that autism can be understood as multiple conditions with distinct trajectories.

              Autism has long been seen as a single—if highly heterogeneous—condition. But rather than one continuous spectrum, there are distinct autism subtypes, each tied to its own genetic signature, a new study suggests.

              The research, published 9 July in the journal Nature Genetics, connects genetic differences to specific patterns in how autism traits appear, supporting the notion that there are “many autisms,” says Michael Lombardo, senior researcher of neurodevelopmental disorders at the Istituto Italiano di Tecnologia in Genoa, Italy, who was not involved in the work.

              Identifying the genes linked to autism subtypes is just the beginning, Lombardo says. The real challenge now, he adds, “is unraveling the biology that stems from those genes.”

              The researchers, led by Olga Troyanskaya, professor of computer science and integrative genomics at Princeton University and deputy director for genomics at the Flatiron Institute in New York City, used a computational model to analyze data on 5,392 autistic children aged 4-18 years and their non-autistic siblings collected through the SPARK study. (The Flatiron Institute and the SPARK datasets used in the study are funded by the Simons Foundation, The Transmitter’s parent organization.) The data include genetic findings and parent-reported information on developmental milestones, cognitive and behavioral traits, co-occurring conditions and family history.

              The machine learning analysis grouped the autistic people into four subtypes based on their genetic signatures and clinical patterns.

              The “Social/behavioral” group—accounting for 37 percent of the sample and whose participants show repetitive behaviors, communication challenges and co-occurring conditions, but few developmental delays—has common genetic variants linked to ADHD and depression, and rare variants in genes active primarily after birth in certain brain cells. Another 19 percent belong to the “Mixed ASD with Developmental Delay” group, which hit many milestones later in development than children without autism but typically don’t have co-occurring conditions such as anxiety and depression; these participants carry many rare, damaging variants—both inherited and new—in genes active during early brain development in utero.

              [The real challenge now] ‘is unraveling the biology that stems from those genes.’ - Michael Lombardo

              Another group, called “Moderate challenges” (34 percent), is distinguished by a developmental pattern similar to the Social/behavioral group, though with less severity; its participants have rare genetic changes in less essential genes, which may explain their mild core autism traits. The 10 percent of children in the “Broadly affected” group, on the other hand, have prominent autism traits from an early age and carry a heavy load of rare mutations in key genes, including targets of a protein involved in fragile X syndrome.

              These genetic differences track with the ages at which children reached certain developmental milestones and their age at autism diagnosis. For example, the groups with variants in early-expressed genes—the Broadly affected and the Mixed ASD with Developmental Delay groups—showed delays in early developmental skills and earlier diagnoses, whereas the group with variants in genes expressed after birth—the Social/behavioral group—had later diagnoses and developmental timelines similar to those of non-autistic children.

              “There are a lot of kids who seem very neurotypical until a bit later in childhood,” says study investigator Natalie Sauerwald, associate research scientist of computational genomics at the Flatiron Institute. “The fact that we were able to find genetics that aligns with that was really surprising.”

              Other research efforts have identified autism subgroups, but none currently offer the definitive take on how to group populations within the autism spectrum—likely because results depend on who’s studied and how, Lombardo says. The new study included children aged 4-18, which increased the sample size but introduced variability, because a preschooler and a teenager are at different developmental stages, he says. His own work, focused on narrower age ranges, has found fewer subtypes, suggesting that different datasets may yield different subtypes.

              In addition, rather than linking genes to single traits as in past investigations, Troyanskaya and colleagues looked at a person’s overall combination of traits.

              The team validated their new findings using data from the Simons Simplex Collection (SSC), which contains information gathered by clinicians. The autism subtypes identified based on parent-reported data were consistent with those found in the SSC, which suggests that the subtypes reflect real differences, Troyanskaya says.

              As more data become available, the identified autism subtypes may be further refined, revealing additional genetic and clinical details within each group, she says.

              More data can validate the findings across diverse populations and adult cases, which could eventually lead to more tailored diagnoses and support in the future, Sauerwald says.

              Thomas Bourgeron, director of the Human Genetics and Cognitive Functions Unit at the Institut Pasteur in Paris, who was not involved in the work, agrees. “Some individuals need medical support, maybe gene therapy, and others need better inclusion in society, better recognition of neurodiversity and so on,” he says.

              However, he adds, a common limitation in autism research is that it focuses too much on clinical data and not enough on real-life experiences, so there’s a need for more practical, long-term information to better understand how autism affects daily life. “We need to have a better idea of the trajectory of these individuals.”

              Fig. 1: Overview of study design and description of identified subclasses.

              Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs | doi:10.53053/BZOX1294