[Human Immunome Project aims to capture immune data from thousands
of people globally]
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SUNDAY SCIENCE: GIANT PROJECT WILL CHART HUMAN IMMUNE DIVERSITY TO
IMPROVE DRUGS AND VACCINES  
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Mitch Leslie
January 2, 2024
Science
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_ Human Immunome Project aims to capture immune data from thousands
of people globally _

, Yale School of Medicine

 

The hepatitis B vaccine is one of the most potent immunizations,
usually providing decades of protection against the deadly liver
virus. But in about 10% of people it doesn’t work, and in 2020, Amy
Huei-Yi Lee, a systems biologist at Simon Fraser University, and her
colleagues set out to determine whether they could predict who would
benefit. The scientists found that data on recipients’ immune
systems
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as the abundance of certain proteins and the activity patterns of a
few genes foretold whether they would generate defenses against the
virus. “We got a sense of what factors drive the vaccine response
and what [doesn’t],” Lee says.

She and her colleagues were only able to take measurements from a
handful of patients, but an ambitious effort slated to begin early
this year will collect such data from hundreds of thousands of
volunteers throughout the world. Called the Human Immunome Project
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international consortium of companies, government agencies, and
universities, the effort will probe thousands of immune variables in
blood and tissue samples. The result will likely be the world’s
largest and most comprehensive immunological database, a resource for
scientists investigating immune system differences and how they
influence our responses to vaccines and drugs and our vulnerability to
illness. “There’s a huge opportunity here in terms of
understanding human disease,” says immunologist Mark Davis of
Stanford University, who is not involved in the project.

And that’s just the start for the effort, which currently operates
on about $5 million a year in funding but could ultimately cost
billions. An offshoot of a previous effort known as the Human Vaccines
Project, HIP will also use the data as fodder for new artificial
intelligence (AI) models that could predict immune system responses
across entire populations, providing valuable insights not just for
pharmaceutical companies and governments, but even for doctors and
patients. “The impacts will be felt globally,” says neuroscientist
Hans Keirstead, the Irvine, California–based project’s CEO.

Scientists unconnected to the project say its goal of compiling a
basic immune database for the world is feasible. “We have the
experience and technology,” says immunologist Allison Greenplate of
the University of Pennsylvania. But she and others question how much
insight AI will add. “There is a lot of low-hanging fruit we don’t
need AI to pick” but that researchers can parse themselves, says
immunologist Paul Thomas of St. Jude Children’s Research Hospital.

In the field of cardiology, a lipid panel reveals a lot about a
patient’s cardiovascular health and risk of disease. Immunology,
however, doesn’t have a comparable set of simple measurements that
indicate the status of a person’s immune system, Davis says. Some
data can provide a rough gauge: Patients with reduced numbers of
neutrophils, for instance, are prone to infections. But such data are
limited. HIP aims to come up with a uniform group of measurements that
can, like a lipid panel, provide a readout of the immune system’s
functioning.

A few public and private efforts have scooped up some basic immune
data from large numbers of people, including All of Us, the U.S.
National Institutes of Health’s program to gather genomic and
medical data from 1 million people, and Project Baseline from the
Google offshoot Verily, which tallied information on how individuals
responded to COVID-19 infection. But such projects have collected
limited categories of information and, in Project Baseline’s case,
haven’t made the data available publicly.

Another area where research has fallen short is “the understanding
of human immune variation and diversity,” says John Tsang, a systems
immunologist at Yale University who helped develop HIP’s scientific
plan. A litany of factors—including age, sex, diet, living
conditions, previous disease exposure, and genetics—shapes how the
immune system functions. But most immunological studies are conducted
on small, homogenous populations, usually in the United States or
Europe, Tsang says. Relying on such a narrow slice of humanity “has
biased our understanding,” Thomas says.

HIP aims to address that lack of diversity. “We want baseline data
from every human population,” Keirstead says. To capture human
variety, HIP’s plans call for up to 300 collection sites on all of
the inhabited continents. Each site will measure the same set of
variables in as many as 10,000 people, from different socioeconomic
levels and a range of ages, from newborns to centenarians. In
addition, they will include healthy people as well as individuals who
have medical problems such as autoimmune diseases, cancer, and
allergies. All volunteers will have to undergo medical exams and
provide a detailed health history.

Although HIP intends to begin this global data collection phase in
2027, the effort’s first phase, launching this year, will be smaller
and likely involve seven to 10 clinical research centers, including
facilities outside the wealthy countries, that are already adept at
gathering and analyzing immune data, Keirstead says. At each site, the
project will study about 500 people, measuring immune variables
including the abundance of different types of immune cells, gene
activity, concentrations of metabolic molecules, and DNA sequences.
“The idea is that we will go deep and measure as much as
possible,” Tsang says. From this mass of data, the project will then
select a few variables that provide the clearest picture of how the
immune system is working. They will also provide the basis for an
immune monitoring kit, a standard set of assays that all the sites in
the second part of the project will use.

In the end, HIP will generate nearly 2 trillion immune measurements,
which will be publicly available through a central database. With this
data haul and other information, HIP will build a predictive AI model
that can forecast—based on immune profile, ancestry, economic
status, age, and other information—how individuals will respond to
stresses or challenges, such as a particular drug or pathogen. The
model could help pharmaceutical companies identify opportunities for
new treatments and drug reactions to avoid. And by providing a much
more detailed view of a population’s health and vulnerability to
side effects, the model could enable countries to better decide which
drugs are needed by and suitable for their populations, thus allowing
them to reduce health care costs, Keirstead says.

What HIP is aiming for with its AI ambitions has “never been done
before,” Kierstead says, which is probably why this part of the
project draws more skepticism from outside researchers. The project
intends to generate not just predictive models, but also ones that
replicate how the immune system operates. Mathematical biologist
Reinhard Laubenbacher of the University of Florida says the AI will
detect patterns of responses but doubts it will open a deeper
understanding of the immune system. “Data collection efforts like
this are tremendously helpful, but we will probably need more than
that,” he says. A priority is “building [a] theoretical
framework” to understand the information the project will accrue, he
says.

Another challenge is money. To realize its ambitions, HIP will require
a supersize budget, about $1 billion to $3 billion over the next 10
years, Keirstead says. To raise the needed funds, HIP now hopes to go
beyond its current partners to philanthropies, governments, and other
pharmaceutical companies. “I am targeting everyone. There is not
going to be a stone left unturned,” he says.

Ensuring that HIP’s far-flung sites follow the same procedures in
collecting and analyzing the data will also be a challenge, Lee says,
adding that the immune monitoring kits will be a big help in this
regard. Thomas says that attracting nonwhite participants could also
be difficult, given their mistrust of scientific research like this.
“They haven’t seen benefits and have been exploited.”

Still, he and others are eager to see what HIP produces. “If they
pull this off, it will be big,” Greenplate says.

_MITCHELL LESLIE _of Albuquerque, N.M., is a frequent contributor
to _Stanford_ and the journal_ Science._

_SCIENCE MAGAZINE. 
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THE MOST MYSTERIOUS CELLS IN OUR BODIES DON’T BELONG TO US
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By KATHERINE J. WU
You carry literal pieces of your mom—and maybe your grandma, and
your siblings, and your aunts and uncles.
THE ATLANTIC
January 3, 2024

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