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’Omics in Translation

’Omics in Translation



While the clinical world has just begun to realize the promise of genomics to inform more precise care for individual patients, scientists also are pushing ahead with the development of clinical tools using other ’omics. The studies of proteins and metabolites—proteomics and metabolomics, respectively—offer considerable promise. In most cases, though, lots of lab work remains to be done before clinicians can benefit from proteomics or metabolomics.

First, the work in both fields is on the rise (See “On the Upswing”). Searches on PubMed revealed that published research on proteomics and metabolomics is increasing in general and in studies with medical and clinical implications.

When it comes to ’omics and medicine, cancer might come to mind first as the most likely application. That’s no surprise, especially since scientists and clinicians started thinking about ’omics-based tools for cancer some time ago. In 2007, for example, researchers from the University of Magdeburg in Germany wrote: “Proteomic studies have generated numerous datasets of potential diagnostic, prognostic, and therapeutic significance in human cancer.”

Despite the great opportunities for proteomic and metabolomic work on cancer care, work from these ’omic areas can also impact other aspects of medicine. From the London-based National Heart and Lung Institute, scientists explored the application of ’omics to heart disease, specifically a kind of high blood pressure called pulmonary arterial hypertension. “High-throughput platforms for plasma proteomics and metabolomics have identified novel biomarkers associated with clinical outcomes and provided molecular instruments for risk assessment,” they wrote. “There are methodological challenges to integrating these datasets, coupled to statistical power limitations inherent to the study of a rare disease, but the expectation is that this strategy will reveal novel druggable targets and biomarkers that will open the way to personalized medicine.”

Suraj Dhungana
Suraj Dhungana
manager of biomedical research global markets, Waters

When asked about the most exciting areas of translational metabolomics or proteomics research, Suraj Dhungana, manager of biomedical research global markets at Waters Corp., said, it “is the ability to take a biomarker or a panel of biomarkers and make it clinically relevant, or applicable, to studying cellular processes in a hypothesis-driven manner. The real strength of this approach depends on the ability to measure biomarkers reproducibly, complete large cohort studies in a timely manner, and identify true stable phenotypic markers, since stable biomarkers are reliable gauges of the phenotype.”

Even with so much to gain from exploring the opportunities in proteomics and metabolomics, some serious challenges remain—even when it comes to assessing the data. As Dhungana noted, the ’omics “literature is plagued by irreproducibility, poorly designed studies with insufficient sample sizes, and attempts to translate a marker that is not very stable or robust.”

Analyzing infections

Scientists face a formidable task to explore even one person’s proteins, because there are about 10 billion of them, according to Hanna Budayeva and Donald Kirkpatrick of Genentech. Still, it’s worth exploring these molecules and what they do, because Budayeva and Kirkpatrick wrote: “As drug development progresses against the next generation of challenging targets, understanding the interconnected protein communities that they participate in is critical.”

The entire world sees right now how critical proteomics might be as every country battles COVID-19. To help researchers around the world study this virus, scientists in China developed the 2019 Novel Coronavirus Resource (2018nCoVR). According to this resource’s developers: “2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC).”

The fast pace of the spreading infection requires fast-paced science to stop the virus. For example, one research team used bioRxiv to quickly publish a protein-protein interaction map for SARS-CoV-2—the agent that causes COVID-19. This large team of researchers—with scientists from France, the U.K., and the U.S.—expressed 26 COVID-19 proteins, identified the human proteins that interact with the virus-related proteins, and used that information to identify 332 high confidence SARS-CoV-2-human protein-protein interactions.

“Among these, we identify 67 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays,” the researchers noted.

This work alone reveals the life-saving potential of translating proteomics research to the clinic.

Metabolomic medicine?

Already, scientists apply metabolomics to many basic questions in research as well as health-related ones, but is it ready for the clinic? To find out, I asked Annie Evans, director of R&D at Metabolon. “One of the unique characteristics of metabolomics is its ability to reveal functionality,” she said. “This is of great benefit as it can help to fill the gaps of other ’omics where insights may be lacking.” She added that scientists can use metabolomics to “provide a bridge with other ’omic approaches to more completely understand disease manifestation and state of the phenotype in the present time.”

Annie Evans
Annie Evans
director of R&D, Metabolon

Getting metabolomics into healthcare, though, will take some time. “There is a lot of work ahead of us to make widespread use of clinical metabolomics a reality,” Evans noted. “The exciting aspect of this work, and why I want there to be a day where all people can have their metabolic profile mapped, is that through this work, we are revealing a wealth of new, meaningful, and actionable information that is shaping our understanding of human disease and treatment, or precision medicine.”

Much of the benefit of metabolomics comes from the breadth of what it can reveal. “Metabolomics provides an assessment of health, whether influenced by genes, the environment, epigenetics, or the microbiome, delivering insight into cause and remediation of disease,” Evans said. “For more than five years, Metabolon has been analyzing the metabolomic profiles of individual patient samples, working directly with clinicians and comparing patient data to established healthy cohorts.”

This work in clinics already provides some real-world health benefits. An example Evans noted was “instances where an individual’s metabolic profile showed that they were not tolerating or processing prescribed medications, indicating that changes were needed to prevent long-term damage.” So, this metabolomic information can be used to help a clinician adjust a patient’s treatment. Work at Metabolon also exposed “cases where the metabolic profile indicated that supplementation would potentially lead to improved quality of life,” Evans said. “These are examples of the profound ways clinical metabolomics can deliver precision medicine to help address and influence human health assessments.”

This global metabolic pathway signature from a patient with the rare disease phenylketonuria (top) and the exact biochemical pathway affected (phenylalanine metabolism, bottom) demonstrate how the elevated phenylalanine due to PKU results in the excess production of phenylalanine-associated microbiome metabolites that further support the PKU phenotype in the patient. CREDIT: Metabolon

Although Evans called those the more dramatic examples, she also indicated that metabolomics could provide many details about an individual’s day-to-day life. This information, she said, “can reveal whether people are being exposed to pesticides even though they eat only organic produce or the intensity of their last workout.”

Some of the most interesting information from metabolomics could involve the unknown. As an example, Evans said that Metabolon has been collecting and analyzing patient samples to better understand the role metabolomics plays in health and how it might be used in more instances in the clinical setting. “Some of our findings have led to answers, directional clues, or biomarkers for patients with difficult-to-diagnose diseases that previously had none,” she added.

Metabolomics is also at the heart of exploring the microbiome. “We can go beyond identifying what organisms are in the microbiome to explaining what they are producing,” Evans said. “The impact they are having on the host is illuminated by identifying the metabolic function of the microbiota species and what is crossing over from the gut, mouth, skin, et cetera, and entering into other systems of the body.”

Exploring the endpoints

Even as genomics continues to dominate much of the biological and medical literature, researchers know there is much more to understanding human health than just the effects of our DNA. “Metabolomics and lipidomics are exciting because they are the endpoint readouts of biological processes,” Dhungana said. “They are downstream of genes and proteins, and thus, closer to the phenotype. Measuring the metabolites or lipids truly gives us insight into the biochemical state of a system.”

To really understand how metabolomics impacts an organism, scientists must think broadly. “We now know that both internal processes and external exposure—chemical, microbiome, food—alter the metabolome and contribute towards the phenotype,” Dhungana stated. “This makes it very exciting as we can develop a holistic view of a disease or a condition using metabolite and lipids as our gauges and start asking complex biologically-relevant questions.”

To answer those questions, scientists need to know what metabolites and lipids a person is producing and how much of them. Today’s technology can also reveal the location of these metabolites and lipids. “For example, if we are looking at tumor metabolism, we can measure the metabolites in and around a tumor micro-environment and generate a spatial distribution profile of metabolites or lipids to better understand the metabolic gradient across the tumor and biochemically map the tumor boundaries,” Dhungana explained. Using desorption electrospray ionization (DESI) mass spectrometry (MS), scientists can “spatially visualize the metabolites and lipids from cross-sections of biological tissue samples,” he said. “DESI imaging is in fact a metabolic phenotyping approach as it provides non-subjective information about the biochemical distribution of molecules after just one measurement without any need for labeling.”

Consider a sample of a tumor. “With DESI imaging, one can map the spatially distributed lipid profile within tumor tissue samples and make a non-subjective classification of tumor and tumor boundaries using molecular ion information to complement current histology-based classification techniques,” Dhungana explained. “If the tumor is treated with small-molecule drugs, one can visualize the distribution of those drug and drug metabolites across the tumor with the data collected from the same experiment.”

Technological progress

The top choices in technology for proteomic and metabolomic studies also depend on the challenge. As Winston Timp of Johns Hopkins University and Gregory Timp of the University of Notre Dame described, a variety of sequencing and microscopic techniques can be applied to proteomics. As they wrote, however: “With the advent of scalable, single-molecule DNA sequencing, genomics and transcriptomics have since propelled medicine through improved sensitivity and lower costs, but proteomics has lagged behind.”

In general, advancing metabolomic and proteomic research to the point of broad use in healthcare will certainly require improvements of many kinds. Sometimes scientists and clinicians “need state-of-the-art technology or a novel approach to probing biology,” Dhungana said. “At other times it might be a clever, high-throughput method that reproducibly measures relevant metabolic markers.” Consequently, gaining clinical use from proteomics and metabolomics will depend on developing the needed balance of available technology and using it in the most effective workflows.

The post ’Omics in Translation appeared first on Clinical OMICs - Molecular Diagnostics in Precision Medicine.

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Rent Control Is A Disaster – Don’t Let It Spread Across The Nation

Rent Control Is A Disaster – Don’t Let It Spread Across The Nation

Authored by Betsy McCaughey via The Epoch Times,

America’s renters -…



Rent Control Is A Disaster - Don't Let It Spread Across The Nation

Authored by Betsy McCaughey via The Epoch Times,

America’s renters - more than one-third of the nation’s households - are in for trouble.

Left-wing politicians are demanding rent regulation from coast to coast. Wherever it is adopted, the result will be a disastrous reduction in the rental housing supply, leaving renters desperate for places to live.

New York is the poster child for the failures of rent regulation. The U.S. Supreme Court is currently mulling a challenge to the constitutionality of the city’s rent regime.

Whatever the justices decide, the public needs to consider less destructive, more targeted ways to help low-income people pay for housing. The court of public opinion needs to consider these facts.

Fact No. 1: Rent regulation isn’t targeted to the poor.

In New York, there’s no means test. What you need is luck or connections. The mean income of a rent-stabilized apartment dweller is $47,000, but census data show that tens of thousands of them earn more than $150,000 per year. Some occupants use what they’re saving on rent to pay for a weekend place in the Hamptons or New England.

The pols don’t object—a sure sign they’re calling for rent regulation to help themselves politically, not the poor.

In New York, 44 percent of rental apartments are regulated by the Rent Guidelines Board (RGB), established in 1969, which sets the maximum amount by which landlords are allowed to raise the rent. Those limits apply to all buildings of six or more units built before 1974.

In 2022, the RGB set the maximum rent hike at 3.25 percent on one-year leases and this year at 3 percent. Never mind that last year, fuel costs to heat the buildings soared by 19 percent and overall inflation hit 8.3 percent.

The decisions are political, not economic. Many Democratic politicians vilify building owners as “greedy landlords” and depict themselves as the champions of the downtrodden. It’s a scam.

Fact No. 2: Winners and losers.

The winners are the lucky few with rent-regulated apartments and the pols who count on an army of tenant activists to turn out at the polls. The losers are the 56 percent of renters who don’t score a regulated apartment and have to scour neighborhoods for an unregulated place that they can afford. They’re paying more.

Why? Because regulation causes some landlords to walk away, reducing the overall supply of apartments. The laws of supply and demand mean rents go up. New Yorkers in unregulated apartments are paying the highest rents in the United States for a one-bedroom apartment. They're the real victims, and they should be furious.

Yet the left-wing press pretends that rent control offers only benefits. The New Republic warns that the Supreme Court challenge threatens “laws that have benefitted the city’s tenants for generations.” Sorry, untrue—only some tenants, and not always the neediest.

It’s economic madness. The saner way to help those who need assistance paying rent is with a voucher. We offer the needy SNAP debit cards to help them pay for groceries. No one slaps price controls on grocery stores or designates certain stores as “regulated,” forcing them to sell at below cost.

Yet New York forces certain landlords to pay what should be a public cost shared by all, an argument made to the court.

Fact No. 3: The Marxist fantasy that rent regulation will help the poor is spreading across the United States and Europe as well.

Maine and Minnesota have enacted laws allowing municipalities to impose rent regulations. In November 2024, California voters will be asked to approve a proposition allowing local governments to add additional restrictions to the state’s existing rent caps.

The laws of supply and demand are international. Berlin froze rents in 2019, and the rental supply plummeted, according to the Ifo Institute, a think tank.

Yet London Mayor Sadiq Khan is calling for freezing rents for two years. London provides housing vouchers to the poor—a smarter approach—but when the city froze the voucher amounts during the COVID-19 pandemic, fewer apartments were available in the price range. The answer is to raise the voucher amount. Freezing rents will only make the shortage worse.

Ignore the demagogues. The evidence is in: Rent regulation is a political scam. There are better ways to help Americans afford a place to live.

Tyler Durden Sat, 10/14/2023 - 16:20

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‘No Regrets’: Former CIA Director Repeats Debunked Russian Disinfo Claims About Hunter’s Laptop

‘No Regrets’: Former CIA Director Repeats Debunked Russian Disinfo Claims About Hunter’s Laptop

In an interview last night with Fox’s Bret…



'No Regrets': Former CIA Director Repeats Debunked Russian Disinfo Claims About Hunter's Laptop

In an interview last night with Fox's Bret Baier, former CIA Director Leon Panetta humiliated himself as he defended the letter that he and 50 other so-called 'intelligence officials' signed suggesting that the Hunter Biden laptop was Russian disinformation.

Even more unsettling were his comments that he believes it could still be Russian disinformation.

“That letter was used in the debate, I haven’t asked you this but do you have regrets about that now looking back, knowing what you know now?” Baier asked.

Panetta explained that he was “extremely concerned about Russian interference” in the run up to the 2020 Presidential Election between then-former-Vice President Joe Biden and then-President Donald Trump.

He claimed that intelligence agencies discovered that “Russia had continued to push disinformation across the board.”

He said that he wanted to “alert the public” about the “disinformation efforts” to influence the election.

“And frankly, I haven’t seen any evidence from any intelligence agency that that was not the case,” Panetta said.

“You don’t think that it was real?” Baier asked.

“I think that disinformation is involved here. I think Russian disinformation is part of what we’re seeing everywhere,” Panetta responded.

“I don’t trust the Russians, and that’s exactly why I was concerned that the public not trust the Russians either.”

And finally, Baier asked if Panetta had any regrets over how he handled the story.

“No, I don’t have any regrets about not trusting the Russians,” Panetta said.

As Jonathan Turley pointed out,Panetta simply refused to acknowledge:

(1) American intelligence quickly debunked the claim and said that there was no evidence of Russian disinformation behind the laptop,

(2) the emails contained in the laptop were quickly authenticated by the other parties,

(3) the FBI authenticated the laptop,

(4) Hunter Biden has since sued over the use of his laptop, and

(5) the media has independently authenticated the laptop.

This was the man in charge of our CIA.

As a reminder, it has also been shown that the Biden campaign and associates coordinated the letter.

Watch the lying liar lie below...

We give the last word back to Turley who summarized the former spook's self-immolation perfectly: "Panetta has become the personification of the economic theory of path dependence. No matter how much countervailing evidence is presented to Panetta, he still refuses to accept the authenticity of the laptop."

However, in order to admit to these facts, Panetta would have had to admit that he was a willing or unwitting dupe of the campaign. It is easier to simply continue to claim that this could all be the invention of the Russians.

Yet, as Turley exclaims, Panetta is still sought for his advice on other intelligence matters as he continues to repeat disproven claims because the truth is simply too costly on a personal level to acknowledge.

What do we call false claims that are repeated despite being repeatedly debunked and disproven? Oh, yea, disinformation.

Tyler Durden Sat, 10/14/2023 - 14:35

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Bibi & Khamenei Trade Social Media Threats As IDF Readies For Air, Ground, & Naval Offensive Against Gaza “Very Soon”

Bibi & Khamenei Trade Social Media Threats As IDF Readies For Air, Ground, & Naval Offensive Against Gaza "Very Soon"

Update (1330ET):…



Bibi & Khamenei Trade Social Media Threats As IDF Readies For Air, Ground, & Naval Offensive Against Gaza "Very Soon"

Update (1330ET): The Israeli military has announced it is prepared for a coordinated air, ground and naval offensive in the Gaza Strip "very soon," according to reports from AP.

In a nationally broadcast address Saturday night, Rear Adm. Daniel Hagari issued a new appeal to residents to move to the southern Gaza Strip.

“We are going to broadly attack Gaza City very soon,” he said.

He accused Hamas of trying to use civilians as human shields.

Meanwhile, the social media rhetoric between leaders has gone to '11'...

Iran's Supreme Leader Khamenei expects a "complete victory"...

Calling on all Muslims to join the fight...

Israeli PM Netanyahu made his views very clear:

Live feeds below on Gaza: 

*  *  *

Israeli media is reporting a "greenlight" has been given for the expected major Israeli offensive on the Gaza Strip as massive convoys of Palestinian civilians have been observed fleeing to the southern part of the densely populated strip. So far there has been limited ground incursions by the army into the strip, targeting Hamas operatives and reportedly to gain intelligence on the whereabouts of hostages. 

The United Nations has issued a report saying at least 423,000 Palestinians have already been internally displaced within Gaza and this massive figure is expected to ratchet further. Likely it has surpassed a half-million as of Saturday, following the Israeli-issued evacuation order, which included dropping thousands of leaflets and warnings over Gaza City. 

Via The Guardian

The UN said it "considers it impossible for such a movement to take place without devastating humanitarian consequences." Middle East Eye and other regional sources have said over 700 Palestinian children were killed in one week of fighting. As of Friday Israel authorities tallied that over 1,300 Israelis were killed by the Hamas terror attacks on the southern settlements and the music festival, and rocket fire, with at least 3,200 wounded. 27 among the dead were Americans.

Middle East Eye on Saturday reports the following of the mounting Palestinian death toll in both Gaza and the West bank as follows:

Israel has killed at least 2,215 people in Gaza over the past week, according to the Palestinian health ministry. Of those killed, 724 are children and 458 are women. Some 8,714 people have been wounded in the besieged enclave in that time, it added. 

Meanwhile, Israeli forces have killed 54 people and wounded 1,100 others in the occupied West Bank.

According to a review of the last hours of developments, the population is about to run out of water as the remaining supply dwindles after Israel cut off external supply sources

  • UN agency for Palestinian refugees says its shelters in Gaza “are not safe anymore” as it warns water running our for besieged enclave’s residents.
  • More than 320 Palestinians have been killed in the past 24 hours, including many women and children killed in Israeli air raids on convoys fleeing Gaza City, according to health officials.
  • The rising toll comes as Israel continues bombing Gaza a day after telling 1.1 million residents to head south ahead of a looming ground offensive following Hamas’s attack inside Israel last week.
  • At least 2,215 Palestinians have been killed and 8,714 wounded in Israeli air attacks on Gaza. The number of people killed in Israel has reached 1,300, with more than 3,400 wounded.
  • In the occupied West Bank, the number of Palestinians killed by Israeli fire in the past week has topped 50. More than 1,000 have been wounded and hundreds arrested.

The fate of the estimated 100 to 200 hostages in Hamas captivity still remains largely unknown, but Hamas in statements which have been underreported in Western press has claimed that over two dozen of the hostages have been killed by the IDF's ongoing aerial bombardment of the Gaza Strip

Hamas' Izz al-Din al-Qassam Brigades said nine more captives were killed in indiscriminate Israeli shelling in the last 24 hours, including a number of foreigners

Qassam has previously announced the death of 17 captives in Israeli air stikes in Gaza over the past week. 

Sky News and others are also reporting, based on Israeli sources, that bodies of hostages have been recovered after some of the initial IDF infantry cross-border raids which began Friday into Saturday:

Raids carried out on the Gaza Strip by Israeli forces discovered human remains of those who had been missing since Hamas's attack last weekend, local media is reporting.

According to Haaretz, armed forces entered an enclave where it is thought up to 200 people were being held hostage by Hamas, and retrieved the bodies of several people.

Items belonging to the missing people were also discovered. 

The US said Friday it chartered its first successful evacuation flight, with talk of more to come.

TOI: A military official at the forensic center at the Military Rabbinate's headquarters in Ramle stands in front of the remains of the victims of Hamas's October 7 shock onslaught in Israel, October 13, 2023. Flash90

There are Americans (many of them likely dual nationals) among the population of Gaza, which Washington says it is trying to facilitate safe exit for as Israeli airstrikes continue. Dangerously, the lone Raffah border crossing into Egypt has at this point been bombed several times. 

But regional media is reporting there's been a diplomatic breakthrough on this front, as Israel, Egypt, and the United States have forged an agreement to let foreigners residing in Gaza pass through the Rafah border crossing into Egypt.

Scene from the frontlines as the IDF build-up outside Gaza continues:

Huge civilian convoys have been witnessed fleeing to the southern half of Gaza, creating bottlenecks...

The Times of Israel cites a senior Egyptian official as follows:

The official says Israel has agreed to refrain from striking areas the foreigners would pass through on their way out of the besieged Palestinian territory. He adds that Qatar was involved in the negotiations and the participants received approval from the Palestinian terror groups, Hamas and Islamic Jihad.

The agreement  does not deal with hostages being held by Hamas.

A second official at the Egyptian side of the Rafah crossing point says they received “instructions” to reopen it on Saturday afternoon for foreigners coming from Gaza.

But Egypt is by and large not letting Gazans exit, even erecting bigger concrete barriers of extra border protection, amid what's setting up to be a catastrophic humanitarian crisis as the Israeli pressure ratchets.

The IDF says it is about to attack the northern half of the Gaza Strip with "great force" - while the US and other countries are urging for caution regarding Palestinian civilians. Below is rare footage of an elite Israeli rescue squad in action (intentionally blurred by IDF sources):

Washington has still all the while said it "stands with Israel" - and has not tried to actually halt the unrelenting IDF bombardment of civilian areas.

Meanwhile, things continue ratcheting in south Lebanon, with reports of new strikes being exchanged between Israel and Hezbollah, and other pro-Palestinian factions.

Tyler Durden Sat, 10/14/2023 - 13:40

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