Trade, finance, and investment are central to achieving a low-carbon global transformation. Trade plays a key role in spreading clean technologies, strengthening supply chains and lowering the cost of climate action. Aligning trade and climate policies can deliver greater emissions reductions per dollar spent by facilitating access to renewable energy goods and services and repurposing environmentally harmful subsidies. Trade policies can also be leveraged to reduce distortions, promote pro-climate goods and services, and accelerate the deployment of green technologies through investment, technology transfer and capacity-building. These combined efforts demonstrate that coherent trade, finance and investment policies are essential to make climate goals achievable and to ensure that the transition supports inclusive and sustainable development.
Continuing these broader efforts to align finance, investment, trade and climate agendas, a high-level session is being organized to showcase how low-carbon and green value chains can support emissions reduction goals, foster climate-resilient growth and unlock trade and investment opportunities in developing countries. With the SDG investment gap exceeding $4 trillion annually – much of it linked to renewable energy and sustainable infrastructure – bridging this financing gap is essential to deliver on Nationally Determined Contributions (NDCs), advancing structural transformation and building competitive low-carbon sectors.
The session will present initiatives that promote decarbonization, economic diversification and the development of sustainable value chains in developing countries. These initiatives are led or supported by international organizations — including UNCTAD and UNDP, as part of their contribution to the Baku Initiative on Climate Finance and Investment for Trade (BICFIT), launched in 2024 under the COP29 Presidency (Azerbaijan), as well as the World Trade Organization (WTO), International Trade Centre (ITC), International Chamber of Commerce (ICC), and other partners. The discussion will also highlight how strategic partnerships — such as public–private partnerships (PPPs), multilateral development banks (MDBs) and development finance institutions (DFIs) — can mobilize private capital and accelerate progress toward sustainable development.
The session will conclude by highlighting concrete examples of how sustainable value chains can advance the implementation of NDC targets and support the transition to low-carbon, climate-resilient economies and SDGs. It will showcase pathways for greener production, economic diversification, and greater inclusion of SMEs in sustainable trade. Participants will also discuss practical mechanisms to scale up investment in sustainable sectors, strengthen technology transfer and capacity-building, and enhance international cooperation. In doing so, the session will illustrate how trade-led approaches can translate climate commitments into tangible development turning trade into an enabler of the Paris Agreement and the Sustainable Development Goals.
Roula Khalaf, Editor of the FT, selects her favourite stories in this weekly newsletter.
Meta is planning to raise $25bn from a bond sale to help it pay for soaring artificial intelligence costs, even as the Big Tech group’s share price fell amid concerns that its spending is too high.
The social media group has hired Citigroup and Morgan Stanley to raise up to $25bn in debt, ranging from five to 40 years in maturity, in what would be one of the biggest bond sales of the year, according to two people close to the matter.
It comes a day after chief executive Mark Zuckerberg warned that the US tech group would spend even more aggressively as part of an arms race to build the data centres and infrastructure powering the AI boom.
Meta’s shares fell 12 per cent after Wall Street’s opening bell on Thursday — wiping out about almost $240bn from its valuation — as investors fretted over the tech group’s huge outlay.
The sale underscores how technology giants are increasingly turning to the debt markets as they spend record sums to build AI infrastructure.
Meta raised $27bn of private debt from credit providers, including Pimco and Apollo, in recent months to fund construction of its huge “Hyperion” data centre in Louisiana. Oracle sold $18bn of bonds in September.
Large tech companies are projected to invest $400bn on AI infrastructure this year, including buying computer chips and building data centres. On Wednesday, Meta, Microsoft and Google’s parent Alphabet all disclosed larger than expected spending plans in the current quarter.
The social media company said capex could hit $72bn by the end of the year and that spending growth would be “notably larger” in 2026, implying a number far in excess of an earlier forecast for $105bn.
Zuckerberg defended huge spending on infrastructure for Meta’s own use. He told analysts on Wednesday that it was “the right strategy to aggressively frontload building capacity” as part of the tech group’s bid to be the first to build artificial superintelligence.
At a recent dinner with US President Donald Trump, Zuckerberg said the company planned to spend $600bn on US data centres and AI infrastructure through 2028.
Meta, Citigroup and Morgan Stanley declined to comment. The bond sale was first reported by Bloomberg.
Andy Jassy, CEO of Amazon, speaks during an unveiling event in New York on Feb. 26, 2025.
Michael Nagle | Bloomberg | Getty Images
Amazon is slated to post results for the third quarter after the closing bell Thursday.
Here’s what analysts polled by LSEG are looking for:
Earnings per share: $1.57
Revenue: $177.8 billion
Wall Street is also looking at other key revenue numbers:
Amazon Web Services: $32.42 billion expected
Advertising: $17.34 billion expected
AWS growth will be a major focus for investors once again, as the company faces intensifying pressure from cloud competitors Google and Microsoft, which also reported quarterly results this week.
Revenue at AWS is projected to expand 18.1% year over year, which is about the same growth rate as the second quarter. Google’s cloud revenue accelerated 34% during the third quarter, while Microsoft Azure recorded growth of 40%.
AWS stumbled last week during an extended outage that lasted more than 15 hours, taking down numerous websites as a result. Microsoft experienced outages in its Azure cloud and 365 services on Wednesday, hours before its scheduled earnings release.
The Amazon unit is also battling the perception that it’s missing out on a flurry of highly lucrative artificial intelligence deals for cloud services.
Anthropic and Google deepened their cloud partnership last week in a deal worth tens of billions of dollars, while Meta has inked hefty cloud deals with Google and Oracle in recent months.
Amazon on Wednesday opened its $11 billion AI data center called Project Rainier, which was first announced last December and is intended to train and run models from Claude chatbot creator Anthropic.
Amazon, which has invested $8 billion in Anthropic, said the startup will use 1 million of its custom Trainium2 chips by the end of 2025.
During last quarter’s earnings conference call, investors grilled Amazon CEO Andy Jassy on AWS growth and AI competition.
Jassy reiterated AWS has a “pretty significant” leadership position in cloud market share, while noting that it’s still “early” days in the AI industry that remains “very top heavy” with a “small number of very large frontier models.”
Amazon’s core retail business will also be top of mind for investors as the company gears up for the start of the holiday shopping period. Amazon said earlier this month it planned to hire 250,000 workers to staff up for peak season, the same number as the last two years.
Adobe Analytics recently projected that online holiday spending in the U.S. will jump 5.3% year over year to $253.4 billion, which is slower than last year, when online sales grew 8.7% over the same period.
During the third quarter, Amazon held its annual Prime Day deals event. Online spending reached $24.1 billion in the U.S. across the four-day stretch in July, according to Adobe, exceeding its estimates and representing growth of 30.3% year over year.
Jassy told investors last quarter that President Donald Trump’s shifting tariff policies haven’t dented demand or driven up prices so far this year.
Amazon’s third-quarter sales are expected to increase 11.9% year over year, compared with growth of 13% in the second quarter.
For the fourth quarter, analysts surveyed by LSEG are projecting sales to reach $208.1 billion, representing growth of 10.8% from a year earlier.
Amazon on Tuesday initiated massive layoffs, cutting about 14,000 roles across nearly every area of the company. Executives hinted that more cuts may be on the way in the new year as the company looks to get leaner, reduce bureaucracy and invest further in AI.
Once the job reductions are complete, they’re expected to be the largest corporate cuts in Amazon’s history, CNBC previously reported. Amazon laid off more than 27,000 employees between 2022 and 2023.
Shares of Amazon have increased 4.9% so far this year, while the Nasdaq is up approximately 24% over the same stretch.
FILE PHOTO: Formula One F1 – United States Grand Prix – Circuit of the Americas, Austin, Texas, U.S. – October 23, 2022 Tim Cook waves the chequered flag to the race winner Red Bull’s Max Verstappen.
Mike Segar | Reuters
Apple reports fiscal fourth quarter earnings on Thursday after the bell.
The fourth quarter, which runs through the end of September, is the first quarter that includes a little more than a week of sales of the new iPhone 17 models.
Analysts have said that early signs are pointing to improved demand for the iPhone 17 models, especially the entry-level and Pro models. Investors will be looking for any color from CEO Tim Cook and CFO Kevan Parekh on the demand they’re seeing for the new devices.
Analysts polled by FactSet expect Apple’s fiscal 2025 to be the first year of iPhone sales growth since 2022.
Apple has also been negatively affected by Trump administration tariffs, although the company has gotten praise from President Donald Trump over its plan to spend $600 billion in the U.S. and boost American semiconductor manufacturing. Apple also announced last week that it was shipping artificial intelligence servers from a factory in Houston.
In July, Apple said it could incur $1.1 billion in tariff costs. Investors will be watching to see if its actual costs came in under its forecast, as well as what tariff costs it sees in the current quarter.
Some investors want to see Apple step up its level of capital expenditure and AI spending. Apple has largely sat out the data center and AI chip investment boom that other large tech companies are spending tens of billions on.
Last quarter, Cook said that it was “significantly” growing its investments in the technology. That will likely show up in the company’s capital expenditures, but commentary from Cook may provide insight into the company’s AI strategy.
Cook will also likely praise the company’s five-year deal with F1 to broadcast its races in the U.S. on Apple TV, the latest development in the company’s sports and media strategy.
Expectations remain high for Cook and Apple. In the June quarter, Apple reported 10% year-over-year revenue growth. For the September quarter, analysts polled by LSEG are expecting 7.7% sales growth.
Here’s what Wall Street is expecting, per LSEG estimates:
EPS: $1.77
Revenue: $102.24 billion
Analysts polled by LSEG expect Apple to guide to $132.31 billion in December quarter sales, and earnings of $2.53 per share.
The dollar climbed to the highest level in three months, propelled by a weakening yen and the Federal Reserve pulling back from additional interest-rate cuts this year.
The Bloomberg Dollar Spot Index rose as much as 0.6%, touching its highest level since Aug. 1, before paring some gains. After the Fed reduced rates by a quarter point as expected on Wednesday, Chair Jerome Powell warned that a cut in December is not a given, curtailing expectations for more cuts this year. The Bank of Japan followed by dampening rate-hike expectations on Thursday, pushing the yen down to an eight-month low.
Jazz has partnered with easypaisa to bring its proprietary AdTech platform, CallPerks, to easypaisa’s digital banking ecosystem. The collaboration underscores Jazz’s commitment to empowering brands with innovative, data-driven solutions that transform how customers experience brand communication.
CallPerks, developed by Jazz, turns routine outgoing calls into opportunities for meaningful engagement by replacing traditional ring-back tones with personalized, real-time audio messages. Through this partnership, easypaisa and its brand partners will be able to use the platform to reach customers with tailored content that strengthens brand recall and drives more effective communication.
Ali Fahd, Head of Jazz Lifestyle Ventures, said, “Being the market leader, Jazz holds a unique position to reach and engage customers through its CallPerks platform. This partnership enables easypaisa to leverage CallPerks’ innovative AdTech capabilities to effectively reach its target audience with personalized, high-impact communication.”
Khurram Warraich, Chief Digital Lending Officer at easypaisa, said: “We are delighted to partner with Jazz on this innovative initiative. CallPerks aligns perfectly with easypaisa’s mission to enhance customer engagement through digital-first experiences. By integrating this platform into our ecosystem, we can provide our customers and brand partners with more relevant, personalized interactions that add value beyond traditional financial services.”
This partnership not only bridges AdTech and fintech but also sets new benchmarks for how businesses can use voice as a channel for real-time customer engagement. By combining Jazz’s technological innovation with easypaisa’s reach in digital banking, the two companies are driving forward a more connected, data-driven future that enhances everyday experiences for millions of Pakistanis.
This week saw the launch of Grokipedia, a large language model-powered online encyclopedia created by Elon Musk. The U.S. billionaire claims the new product is a less “biased” alternative to Wikipedia, the decades-old reference site widely seen as one of the last surviving relics of a healthier, more democratic Internet. However, users have found much of Grokipedia’s content to be less than neutral, often promoting the same right-wing views that became more prevalent on X after Musk bought Twitter. If the concept of an AI-“enhanced” Wikipedia alternative with a heavy editorial hand sounds familiar, that’s because the Kremlin already launched one months ago. Meduza compares Grokipedia to Russia’s homegrown reference site, Ruwiki, and examines how they each treat certain politically charged topics.
Drawing from the OG
Ruwiki, first launched in beta in the summer of 2023, is essentially a fork of the Russian-language Wikipedia, meaning it’s largely based on its predecessor’s articles. The main difference — besides its AI capabilities, which were added later — is that Ruwiki articles about topics that are politically sensitive in Russia have been heavily censored. In 2024, the outlet T-invariant reported that most of Ruwiki’s articles about apolitical topics “are copied word-for-word from Wikipedia.”
Grokipedia also appears to be something of a Wikipedia fork. Many of its entries include the disclaimer: “The content is adapted from Wikipedia, licensed under Creative Commons Attribution-ShareAlike 4.0 License.” According to NBC News, some entries are copied verbatim from Wikipedia.
Much like Ruwiki, the Grokipedia articles that differ most from their Wikipedia counterparts are the ones about its creators’ pet issues. For example, as NBC notes, while the Wikipedia article for U.S. President Donald Trump includes a section on potential conflicts of interest, the Grokipedia entry omits many of his highest profile corruption allegations.
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AI Integration
Ruwiki is integrated with YandexGPT, the AI chatbot created by Russian tech giant Yandex. The encyclopedia’s homepage looks more like that of ChatGPT than Wikipedia, consisting of a text field underneath the question “What do you want to learn?” After the user enters a question, Ruwiki provides an AI-generated response based on its body of content, linking to specific articles that it cites.
YandexGPT is itself heavily censored, giving vague and evasive responses to user questions about politically sensitive topics such as the war in Ukraine or the late Russian opposition leader Alexey Navalny.
Grokipedia’s home page is also minimalistic, with a dark color scheme and a single text field. However, rather than an AI-generated response, queries there return a list of related Grok articles, which have themselves been generated and “fact-checked” by Grok, Musk’s AI chatbot.
Grok has repeatedly made headlines this year for pushing conspiracy theories, praising Hitler, and denying the Holocaust in its interactions with users on X (previously Twitter). At one point, it began mentioning “white genocide” in South Africa in responses to unrelated user posts throughout the platform, explaining in one case that it had been “instructed” to do so.
‘Commitment to providing facts without bias’ Russia’s flagship AI chatbot recommends reading Meduza and other ‘foreign agents’
‘Commitment to providing facts without bias’ Russia’s flagship AI chatbot recommends reading Meduza and other ‘foreign agents’
Ukraine war coverage
Grokipedia’s article on Russia’s full-scale war in Ukraine is far less blatantly propagandistic than that of Ruwiki. However, unlike Wikipedia, Grokipedia featurescommon Russian propaganda talking points more prominently and generally assigns them equal weight to evidence-based claims.
The Ruwiki entry, which is titled “Hostilities in Ukraine,” adheres closely to Moscow’s official narratives surrounding the war in Ukraine. Its opening sentence defines the conflict as “an indirect military confrontation between Russia and the United States and NATO.” Subsequent paragraphs suggest the war is a direct consequence of NATO expansion in Eastern Europe; Ukraine’s Maidan Revolution, which it refers to as a Western-backed coup; and a “military operation” by Kyiv “against the population of Donbas.” Overall, the article consistently frames Russia’s invasion as a defensive operation against the aggression of Western countries.
Grokipedia’s entry, on the contrary, acknowledges that Russia “initiated a full-scale invasion” and attempted to instigate regime change in Ukraine in 2022. At the same time, for all its purported neutrality, Grokipedia’s framing of the conflict often amounts to false balance, presenting easily refutable Russian disinformation as merely another “perspective” on the war.
For example, the second sentence of the more than 11,000-word article notes that Russia argues its “special military operation” is “aimed at demilitarizing and denazifying Ukraine” and “protecting ethnic Russians and Russian speakers from alleged persecution in Donbas,” but fails to mention that there was no systematic persecution of Russians or Russian speakers in the Donbas or that there are no “Nazis” in power in Ukraine.
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‘Gender ideology’
While both Elon Musk and the Kremlin have framed the existence of transgender people as an unnatural phenomenon or conspiracy pushed by U.S. left-wing elites, Grokipedia’s entry for “Transgender” editorializes much more and differs more dramatically from Wikipedia than Ruwiki’s.
The Ruwiki article is largely copied directly from Russian-language Wikipedia, though some sentences appear to have been removed, such as: “Transgender identity is not a disease or a disorder.” Grokipedia’s entry, on the other hand, repeatedly suggests that transgender identity is a “social contagion” and that gender affirming care is more harmful than the medical establishment claims. It also devotes more attention to comorbidities with gender dysphoria, pointing to studies that have found a higher prevalence of autism, depression, and anxiety among transgender people than among cisgender people. While it lists “critiques of innate gender identity models” among multiple “theories of causation” for “transgender identification,” it asserts that “philosophically,” this theory “invites circularity” and “conflates belief with biology.”
Both encyclopedias include sections about religious views on transgender identity. However, the Ruwiki article does not make overarching statements about the overall attitude of major religions towards transgender people, instead quoting statements from religious bodies and leaders criticizing the concept of gender identity. In contrast, the corresponding section in Grokipedia asserts: “Major world religions predominantly view transgender identity and transitions as incompatible with divine creation of binary biological sex.”
Dear leaders
Compared to Wikipedia, both Grokipedia’s and Ruwiki’s articles for their countries’ respective presidents omit significant negative information about them. Most of Ruwiki’s entry about Russian President Vladimir Putin reads like an article from Russian state media or from the Kremlin’s official website. However, it does briefly mention the International Criminal Court’s arrest warrant for Putin, noting that Russia does not recognize the court’s jurisdiction. It also includes two sentences about the Kursk submarine disaster in 2000, noting that the incident “prompted criticism not only toward the leadership of the Russian Navy but also toward the president himself.”
Even the “criticism” section of the Ruwiki article on Putin consists largely of compliments from foreign leaders, such as U.K. politician Nigel Farage’s statement that he dislikes the Russian president as a person but admires him “as a political operator.”
A useless add-on Russia’s Wikipedia replacement is touting its integrated AI — but the results are underwhelming
A useless add-on Russia’s Wikipedia replacement is touting its integrated AI — but the results are underwhelming
Grokipedia’s entry on Putin is less fawning but repeatedly takes the Kremlin’s own statements at face value. For example, the article lists a number of past political assassinations of Putin’s critics and enemies, but describes Russia’s failure to prosecute “alleged organizers” as “fueling debates over higher-level complicity.” Notably, the Grokipedia article does not mention the International Criminal Court’s arrest warrant for Putin over the illegal deportation of Ukrainian children.
Ruwiki is more willing to criticize Donald Trump, noting (unlike Russian-language Wikipedia) in its second sentence that Trump is “the first former U.S. president in history to be convicted of a criminal offense.” Also, unlike Wikipedia, the Ruwiki article includes an entire section on Trump’s relationship with the late financier and convicted sex offender Jeffrey Epstein.
Grokipedia avoids mentioning many of Trump’s major scandals, including his relationship with Epstein, the 2024 court ruling that he defamed E. Jean Carroll in comments denying her accusations of sexual assault, and the numerous corruption allegations against him.
CEF Energy is contributing to the development of Europe’s CO₂ networks by funding key transport infrastructure, a central element of the EU’s Industrial Carbon Management Strategy. Since 2019, the programme has invested over €978 million in 28 projects, covering both studies and works across the full CO₂ transport chain – including pipelines, liquefaction terminals, buffer storage sites, and compressor facilities. By linking industrial emitters to permanent storage locations, these projects play a crucial role in reducing industrial emissions and advancing towards climate neutrality by 2050.
New supported CO₂ projects
Following the 2024 CEF Energy call for proposals for Projects of Common Interest (PCI) and Projects of Mutual Interest (PMI), the promoters of ten CO₂ projects have signed Grant Agreements with CINEA in 2025, further expanding Europe’s carbon dioxide transport networks. Together, these actions represent an EU investment of around €240 million, covering three construction works projects and seven preparatory studies. They aim to advance detailed design studies, strengthen cross-border connections and facilitate access to underground storage , with the aim to accelerate the development of new infrastructure that will enable the safe transport of captured CO₂ from industrial clusters to permanent storage sites.
Examples of these new projects include the Prinos project in Northern Greece, which received nearly €120 million to develop a CO2 import terminal and upgrade offshore facilities to create the first carbon capture and storage value chain in the South-Eastern Mediterranean region; the North Sea L10 CO2 facility on the Dutch continental shelf, awarded €55 million for the construction of an offshore spurline connecting to the Aramis project; and the Norne CO2 facility in Denmark, granted almost €12 million for construction of the extension of quay walls in the Port of Aalborg within the first implementation phase of the PCI. For studies, the Baltic CCS projectis preparing the development of a cross-border CO₂ transport network linking industrial emitters in Latvia and Lithuania to a liquid CO₂ terminal in Klaipėda (Lithuania). CEF support contributes to technical, environmental and economic studies to assess the feasibility and design of the terminal and the wider CO₂ value chain.
Together, these ten projects represent an important step towards the necessary European CO₂ infrastructure supporting the 2030 target of 50 million tonnes of annual CO2 injection capacity outlined in the Net Zero Industry Act. They complement earlier initiatives, extend the reach of the carbon dioxide network to new regions, and highlight the EU’s firm commitment to advancing industrial decarbonisation.
Success story paving the way
Several CEF Energy supported projects are already demonstrating how EU funding is turning CO₂ infrastructure plans into reality. Among them, Porthos stands out for its maturity, progress and impact, showing how coordinated European action is building a connected CO₂ transport and storage system.
The Porthos project, coordinated by the Port of Rotterdam and implemented together with Gasunie and EBN, is developing an open access, cross-border network to transport CO2 from industrial sources in the port areas of Rotterdam, Antwerp and Ghent to offshore storage locations in the North Sea. CEF supports the construction of a 33 km long onshore pipeline connecting emitters in the port of Rotterdam, a compressor station of 20 MW located at Aziëweg, and a 20 km offshore pipeline that will transport the compressed captured CO2 to depleted gas fields for storage in the Dutch section of the North Sea. Implemented as part of the PCI CO2 TransPorts, Porthos is expected to be operational in 2026, and illustrates how public-private investments and cooperation can drive large-scale climate solutions.
Building synergies across EU programmes
The deployment of CO₂ transport infrastructure in Europe relies on strong complementarities between EU funding programmes managed by CINEA. While Horizon Europe supports research and innovation for new or improved technologies and the Innovation Fund finances large-scale industrial decarbonisation projects that generate the captured CO₂ to be transported and stored, CEF Energy focuses on developing networks and infrastructures with a cross-border dimension to allow the transport of CO2 from emitters and sources towards permanent geological storage. Together, all three funding programmes support a coherent value chain – from carbon capture to transport and permanent storage – essential to achieve climate neutrality.
One clear example of this complementarity can be seen between the projects Northern Lights (supported by CEF Energy) and Beccs Stockholm (supported by the Innovation Fund). BECCS is building one of the world’s largest facilities for capturing and permanently storing biogenic CO2 in Sweden. This CO2 needs to be safely stored, which is where Northern Lights comes in, as it will enable the storage of up to 900,000 tonnes of biogenic CO2 annually from Stockholm Exergi, while also offering additional CO2 storage capacity (up to 5 Mtpa in total) for other European emitters. A positive Final Investment Decision (FID) was reached by the promoters of these projects in March 2025.
CINEA promotes close coordination and knowledge exchange between project promoters and programme teams, helping to identify synergies, avoid overlaps and accelerate progress across funding instruments. This collaborative approach reinforces Europe’s Industrial Carbon Management ecosystem, ensuring that EU investments deliver maximum impact for a competitive, connected, and climate-neutral Europe.
More information
Interactive publication on EU funding to the Industrial Carbon Management
We developed OpenSpliceAI to be a modular Python toolkit designed as an open-source implementation of SpliceAI, to which we added several key enhancements. The framework replicates the core logic of the SpliceAI model while optimizing prediction efficiency and variant effect analysis, such as acceptor and donor gains or losses, using pre-trained models. Our benchmarks show substantial computational advantages over SpliceAI, with faster processing, lower memory usage, and improved GPU efficiency (Figure 2B, Figure 2—figure supplement 6). These improvements are driven by our optimized PyTorch implementation that employs dynamic computation graphs and on-demand GPU memory allocation – allowing memory to be allocated and freed as needed – in contrast to SpliceAI’s static, Keras-based TensorFlow approach, which pre-allocates memory for the worst-case input size. In SpliceAI, this rigid memory allocation leads to high memory overhead and frequent out-of-memory errors when handling large datasets through large loop iteration prediction. Additionally, OpenSpliceAI leverages streamlined data handling and enhanced parallelization through batch prediction and multiprocessing, automatically distributing tasks across available threads. Together, these features prevent the memory pitfalls common in SpliceAI and make OpenSpliceAI a more scalable and efficient solution for large-scale genomic analysis.
It is important to note that even though OpenSpliceAI and SpliceAI share the same model architecture, the released trained models are not identical. The variability observed between our models and the original SpliceAI – and even among successive training runs using the same code and data – can be attributed to several sources of inherent randomness. First, weight initialization is performed randomly for many layers, which means that different initial weights can lead to distinct convergence paths and final model parameters. Second, the process of data shuffling alters the composition of mini-batches during training, impacting both the training dynamics and the statistics computed in batch normalization layers. Although batch normalization is deterministic for a fixed mini-batch, its reliance on batch statistics introduces variability due to the random sampling of data. Finally, OpenSpliceAI employs the AdamW optimizer (Loshchilov and Hutter, 2019), which incorporates exponential moving averages of the first and second moments of the gradients. This mechanism serves a momentum-like role, contributing to an adaptive learning process that is inherently stochastic. Moreover, subtle differences in the order of operations or floating-point arithmetic, particularly in distributed computing environments, can further amplify this stochastic behavior. Together, these factors contribute to the observed nondeterministic behavior, resulting in slight discrepancies between our trained models and the original SpliceAI, as well as among successive training sessions under identical conditions.
OpenSpliceAI empowers researchers to adapt the framework to many other species by including modules that enable easy retraining. For closely related species such as mice, our retrained model demonstrated comparable or slightly better precision than the human-based SpliceAI model. For more distant species such as A. thaliana, whose genomic structure differs substantially from humans, retraining OpenSpliceAI yields much greater improvements in accuracy. Our initial release includes models trained on the human MANE genome annotation and four additional species: mouse, zebrafish, honeybee, and A. thaliana. We also evaluated pre-training on mouse (OSAIMouse), honeybee (OSAIHoneybee), zebrafish (OSAIZebrafish), and Arabidopsis (OSAIArabidopsis) followed by fine-tuning on the human MANE dataset. While cross-species pre-training substantially accelerated convergence during fine-tuning, the final human splicing prediction accuracy was comparable to that of a model trained from scratch on human data. This result indicates that our architecture seems to capture all relevant splicing features from human training data alone and thus gains little or no benefit from cross-species transfer learning in this context (see Figure 4—figure supplement 5).
OpenSpliceAI also includes modules for transfer learning, allowing researchers to initialize models with weights learned on other species. In our transfer learning experiments, models transferred from human to other species displayed faster convergence and higher stability, with potential for increased accuracy. We also incorporate model calibration via temperature scaling, providing better alignment between predicted probabilities and empirical distributions.
The ISM study revealed that OSAIMANE and SpliceAI made predictions using very similar sets of motifs (Figure 6B). Across several experiments, we note that SpliceAI exhibits an inherent bias near the starts and ends of transcripts which are padded with flanking Ns (as was done in the original study), predicting donor and acceptor sites in these boundaries with an extremely high signal that disappears when the sequence is padded with the actual genomic sequence. For example, the model correctly predicted the first donor site of the CFTR gene when the gene’s boundaries were flanked with N’s; however, when replaced those N’s with the actual DNA sequence upstream of the gene boundary, the signal all but disappeared, as seen in Figure 6D. This suggests a bias resulting from the way the model is trained. In our ISM benchmarks, we thus chose not to use flanking N’s unless explicitly recreating a study from the original SpliceAI paper.
Additionally, we note that both the SpliceAI and OSAIMANE ‘models’ are the averaged result of five individual models, each initialized with slightly different weights. During the prediction process, each individual model was found to have discernibly different performance. By averaging their outputs leveraging the deep-ensemble approach (Fort et al., 2019; Lakshminarayanan et al., 2017), the overall performance of both SpliceAI and OpenSpliceAI improved while reducing sensitivity to local variations. In essence, this method normalizes the inherent randomness of the individual models, resulting in predictions that are more robust and better represent the expected behavior, ultimately yielding improved average performance across large datasets. OpenSpliceAI’s ‘predict’ submodule averages across all five models by default, but it also supports prediction using a single model.
In summary, OpenSpliceAI is a fully open-source, accessible, and computationally efficient deep learning system for splice site prediction. Its modular architecture, enhanced performance, and adaptability to diverse species make it a powerful tool for advancing research on gene regulation and splicing across diverse species.
Novo Nordisk has launched a surprise $9bn (£6.9bn) offer for the US obesity-focused biotech firm Metsera that could gazump an existing bid from Pfizer as the pharmaceutical giants fight for dominance in the weight-loss market.
The bid comes weeks after Metsera agreed to a $7.3bn takeover from the US group Pfizer. Denmark’s Novo Nordisk, which owns the weight-loss drugs Ozempic and Wegovy, lost out in a competitive auction processin September.
Pfizer criticised the unsolicited bid, accusing Novo Nordisk of making a “reckless” offer and claiming it was “an attempt by a company with a dominant market position to suppress competition in violation of law by taking over an emerging American challenger”.
Pfizer now has just four business days to sweeten its offer for the American upstart, which listed on the Nasdaq index earlier this year.
Metsera is seen as a lucrative takeover target in part because of its promising pipeline of obesity drugs. The company has four ongoing clinical trials, including a weight-loss pill, a monthly injection, and two drugs that promote feelings of fullness using the hormone amylin. Some researchers say amylin could avoid the kind of muscle loss that has been a problem with existing medications.
Novo Nordisk has offered $56.50 a share for Metsera, valuing the company at about $6.5bn. It offered a further $21.25 a share, worth about $2.5bn, if Metsera hits specific clinical and regulatory targets.
Novo Nordisk said in a statement that the takeover “would be in line with Novo Nordisk’s long-term strategy of developing innovative and differentiated medicines and treating millions more people living with obesity and diabetes and their associated comorbidities”.
Metsera said Novo Nordisk’s bid was “superior” to the existing bid from Pfizer, which offered $47.50 a share, and a further $22.50 for hitting additional milestones.
But Pfizer said the Danish firm’s offer was set up in a way that was intended to “to circumvent antitrust laws” and “carries substantial regulatory and executional risk”. It also rejected the suggestion that the bid was superior to its own, calling it “illusory”. Pfizer said it was “prepared to pursue all legal avenues to enforce its rights under its agreement”.
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Novo Nordisk has been battling a slowing rate of profit growth and a drop in its share price, particularly after losing ground to its US rival Eli Lilly, which makes the Mounjaro and Zepbound injections. Clinical studies have shown that Mounjaro is more effective in causing weight loss than Wegovy.
Eli Lilly raised its own full-year guidance on Thursday, as third-quarter revenue from those weight-loss and diabetes drugs beat forecasts. The company said it was still planning to put forward its own weight-loss pill to regulators by the end of the year.