Upload XCell normalized payload

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@@ -310,3 +310,5 @@ scPeturb/model_ready/genepert/papalexi2021__thp1__pooled_stimulated.h5ad filter=
 scPeturb/model_ready/genepert/replogle2022__k562_essential_day6.h5ad filter=lfs diff=lfs merge=lfs -text
 scPeturb/model_ready/genepert/replogle2022__k562_genome_wide_day8.h5ad filter=lfs diff=lfs merge=lfs -text
 scPeturb/model_ready/genepert/replogle2022__rpe1_day7.h5ad filter=lfs diff=lfs merge=lfs -text
+xcell/model_ready/genepert/xatlas_orion__hct116__crispri__day7.h5ad filter=lfs diff=lfs merge=lfs -text
+xcell/model_ready/genepert/xatlas_orion__hek293t__crispri__day7.h5ad filter=lfs diff=lfs merge=lfs -text

xcell/LICENSE.md

@@ -0,0 +1,437 @@
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xcell/PROCESSING.md

@@ -0,0 +1,129 @@
+# X-Atlas/Orion 处理流程
+
+## 1. 纳入边界
+
+本来源使用 Xaira Therapeutics 官方发布的 `X-Atlas/Orion`，而不是尚未提供
+payload 的 `X-Atlas/Pisces` 页面。Orion 包含两个独立的人源 genome-wide
+CRISPRi Perturb-seq 背景：HCT116 和 HEK293T。两者始终分别记录为训练单元，
+不跨细胞背景合并细胞或 control。
+
+- 官方仓库：`Xaira-Therapeutics/X-Atlas-Orion`
+- 固定 revision：`53a5bc98d49247bcf967500292575c3d3602de31`
+- 数据页：<https://huggingface.co/datasets/Xaira-Therapeutics/X-Atlas-Orion>
+- 实验论文：<https://doi.org/10.1101/2025.06.11.659105>
+- 作者 processed H5AD 归档（仅作交叉证据，未下载）：
+  <https://doi.org/10.25452/figshare.plus.29190726>
+- 许可：CC BY-NC-SA 4.0
+- HCT116：109 个 Parquet shard
+- HEK293T：223 个 Parquet shard
+- 原始矩阵：作者明确标注的 UMI raw counts
+- 物种：human（GRCh38 2024-A）
+
+大文件下载运行时同时清除大小写两套 HTTP/HTTPS/ALL proxy 环境变量。若
+`huggingface.co` 裸直连 DNS/路由不可用，则使用可直连的公网 Hugging Face
+镜像 endpoint；这仍是 proxy-off 下载，并在下载状态 JSON 中记录 endpoint、
+revision、shard 数和字节数。
+
+## 2. 细胞和扰动筛选
+
+只纳入作者字段 `pass_guide_filter == 1` 的细胞，即包含来自同一 guide pair、
+靶向同一基因的两条有效 sgRNA。以下字段直接来自作者数据，不用正则推断：
+
+- `gene_target`：扰动基因的官方 gene symbol；
+- `guide_target`：双 guide identity；
+- `sample`：GEM batch；
+- `gene_target == "Non-Targeting"`：唯一 control/reference 规则；
+- `gene_token_id` + `gene_expression`：非零基因及 raw UMI counts。
+
+作者只提供 GEM batch，没有可独立解释为生物学重复的 replicate ID；因此
+`batch_id` 保留 `sample`，而 `replicate`/`replicate_id` 留空，不能把技术 batch
+冒充 biological replicate。
+
+论文 Methods 记录两种细胞均以 MOI 0.1 转导、在转导后第 3–5 天进行
+puromycin selection，并在
+第 7 天进入 10x 单细胞测序；因此标准字段固定为
+`context=day7_post_transduction`、`perturbation_duration_h=168`，unit ID 也显式
+包含 `day7`，同时保存 `multiplicity_of_infection=0.1`，不以 `unknown` 或泛化的
+basal context 代替。
+
+论文报告 HCT116 与 HEK293T 的 median on-target knockdown 分别为 75.4% 和
+51.5%，NTC batch 间 median Spearman correlation 分别约为 0.993 和 0.988。
+这支持在各自 cell context 内显式使用 batch covariate，但不能据此把两种细胞
+合并为一个训练单元。作者还指出 sgRNA abundance 与 knockdown 强度相关；本版
+保留 guide identity 和原始 `num_features`，但源 Parquet 不含逐细胞 guide UMI
+数，因此不伪造连续 perturbation-dose 字段。
+
+标准化后，perturbed `condition` 和 `target_gene_symbol` 均使用官方 gene
+symbol；Non-Targeting 细胞统一为 `condition=ctrl1`、`is_control=true`、
+`is_reference=true`、`control_type=non_targeting_guide`。每个 batch 必须实际
+存在 Non-Targeting reference anchor，否则整个训练单元停止并标记 blocked，
+不允许跨 batch 硬配 control。
+
+## 3. 基因和表达矩阵
+
+`metadata/gene_metadata.parquet` 提供 token、Ensembl ID 和可用的官方 gene
+symbol映射。重复gene symbol在同一细胞内按raw count求和；来源没有symbol的
+feature保留Ensembl ID作为`var_names`回退。每个最终文件共38,584个唯一feature，
+其中12,962个为`ENSG...`回退；`var`同时保留来源Ensembl ID、token和折叠数量。
+标准H5AD语义为：
+
+- `layers["counts"]`：确认的 raw UMI counts；
+- `X`：每个细胞 `normalize_total(target_sum=1e4)` 后的 natural `log1p`；
+- `var_names`：文件内唯一，官方gene symbol优先、缺失时Ensembl ID回退；
+- `var[ncounts,ncells,sum_squared_counts]`：由全量 raw counts 精确累计；
+- `obs_names`：`<training_unit_id>::<source_cell_id>`。
+
+转换按 shard 流式执行，不把全基因矩阵整体载入 RAM。每个 shard 完成后将
+`n_obs`、`nnz`、基因矩和 obs 分片作为一个事务提交；中断重启时先把 HDF5
+截断到最后一次完整提交。`X` 和 `layers["counts"]` 使用相同 CSR sparsity，
+其 `indices`/`indptr` 通过 HDF5 hard link 共享，raw 和 log1p data 仍分别保存。
+
+## 4. scVI 表征
+
+每个最终 H5AD 独立训练 scVI，不跨 HCT116/HEK293T 共享 latent space。
+
+- 输入：`layers["counts"]`；
+- HVG：4000；从全量 raw-count 精确一阶/二阶矩计算分箱标准化 dispersion；
+- batch key：`batch_id`（严格等于作者 `sample`）；
+- model：SCVI，NB likelihood，2 layers，128 hidden，30 latent；
+- 输出：逐细胞 `obsm["X_scVI"]`；
+- provenance：`uns["cellclip_scvi"]` 和 `manifest/SCVI_RUNS.tsv`。
+
+HVG counts 被流式抽取成 memory-mapped CSR，避免载入其余约 3.8 万基因。两个
+cell context 可分别占用 GPU 并行训练，但 CPU affinity 总计不超过 56 核，
+也不并发写同一个 H5AD。
+
+## 5. Modeling centers 与 OT
+
+完成 scVI 后，两单元进入与 scPerturb/PerturBase 完全相同的 modeling 流程：
+
+1. 每个单元只保留 HVG5000；
+2. control 分布和每个 perturbed condition 分别在 `X_scVI` 中聚类；
+3. 原始细胞数 `n < 64` 时固定一个中心；
+4. `n >= 64` 时中心数必须使 `64 <= n/k <= 200`；
+5. 中心表达为成员 raw counts 求和后 CP10K natural log1p，不是单细胞均值；
+6. 保存 within-cluster、between-center、condition-neighbor 和 control-effect
+   异质性；
+7. 在 GPU 上用带成员权重的 log-Sinkhorn OT，将每个 perturbed center 固化为
+   一个 `paired_control_index`；
+8. 输出独立 control-center H5AD 和 perturbed-center H5AD，后者保存 OT mass、
+   probability、cost、solver 和配对状态。
+
+超大稀疏 counts 不整体读入内存：HVG5000 使用转换阶段保存的精确 gene
+moments 选择，伪 bulk 按 CSR 行块聚合。
+
+## 6. 必须通过的验证
+
+- 输入细胞数 = control cells + perturbed cells；
+- 每个分布成员数在中心间守恒；
+- 每个正常分布压缩率在 64–200，sub-64 例外恰好一个中心；
+- 所有 HVG 的 source raw-count 总和与所有中心 `sum_counts` 严格相等；
+- `X` 可由 `sum_counts` 的 CP10K natural log1p 重建；
+- `X_scVI` 行数和 30 维 latent 完整且 finite；
+- 所有 paired index 位于对应 control 文件范围内；
+- 不存在无安全 reference 时的跨 batch 配对；
+- manifest、状态 TSV/JSON 和实际 H5AD 数量、行数、字节数一致。
+
+最终 upload-ready 清理只保留标准化 H5AD、modeling center H5AD、机器 manifest
+及本处理/使用文档；官方 raw Parquet、下载缓存、scVI memory map、临时 obs
+分片和论文 PDF 在校验完成后删除。

xcell/README.md

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+# XCell / X-Atlas Orion 发布说明
+
+本目录收录 Xaira Therapeutics `X-Atlas/Orion` 的两个人源 CRISPRi
+Perturb-seq 训练单元。HCT116 与 HEK293T 的实验背景、batch anchor 和 scVI
+空间不同，因此始终分别保存、分别建模，不把细胞跨文件混合。
+
+| 训练单元 | 细胞 | Non-Targeting reference | perturbed | gene condition | GEM batch | 基因 |
+| --- | ---: | ---: | ---: | ---: | ---: | ---: |
+| HCT116, day 7 | 3,409,169 | 165,777 | 3,243,392 | 18,293 | 109 | 38,584 |
+| HEK293T, day 7 | 4,534,299 | 218,838 | 4,315,461 | 18,311 | 223 | 38,584 |
+| **合计** | **7,943,468** | **384,615** | **7,558,853** | **36,604（逐单元求和）** | **332** | — |
+
+| 训练单元 | control centers | perturbed centers | paired | unmatched | 整体压缩 |
+| --- | ---: | ---: | ---: | ---: | ---: |
+| HCT116, day 7 | 869 | 25,921 | 25,921 | 0 | 127.25× |
+| HEK293T, day 7 | 1,700 | 31,665 | 31,665 | 0 | 135.90× |
+| **合计** | **2,569** | **57,586** | **57,586** | **0** | **132.05×** |
+
+最终单细胞文件位于 `model_ready/genepert/`。其 `layers["counts"]` 是作者
+发布的 raw UMI count，`X` 是逐细胞 CP10K 后 natural `log1p`。`var_names` 在
+文件内唯一：官方 gene symbol 优先，来源缺失symbol的12,962个feature以Ensembl
+gene ID回退；30维per-file scVI表征位于 `obsm["X_scVI"]`。
+
+供配对训练直接使用的 HVG5000 多中心文件位于 Stage 1 的统一目录：
+
+- `modeling/control_centers/XCell/genepert/`
+- `modeling/perturbed_centers/XCell/genepert/`
+
+perturbed center 通过 `paired_control_index` 指向同一训练单元 control 文件的
+零基行号。不同 H5AD 的 scVI latent 不共享坐标系，不能跨 HCT116/HEK293T
+重新按 latent 距离配对。
+
+## 数据边界
+
+- 只纳入作者 `pass_guide_filter == 1` 的细胞。
+- `gene_target == "Non-Targeting"` 是直接来自作者字段的唯一 reference 规则，
+  不是由条件名正则推测。
+- perturbed condition 与 `target_gene_symbol` 均为作者发布的官方 gene symbol。
+- effect cell 的 `target_gene_symbol_status="official_source_gene_symbol"`；这表示
+  来源字段是官方symbol，但使用具体基座模型时仍须检查其是否存在于模型vocab。
+- `sample` 保存为 `batch_id`；它代表 GEM batch，不被冒充为 biological
+  replicate。每个 batch 均验证有 Non-Targeting anchor。
+- 两个单元均为 day 7、MOI 0.1；该实验 context 已写入 H5AD 和总 manifest。
+- 原始来源许可为 CC BY-NC-SA 4.0；再发布和商用边界必须遵循原许可。
+
+完整转换、断点恢复、scVI、聚类、异质性与 OT 规则见
+[PROCESSING.md](PROCESSING.md)。训练选择和所有文件的权威统计分别以
+`../manifest/TRAINING_UNITS.tsv`、`../manifest/SCVI_RUNS.tsv` 与
+`../modeling/manifest/MODELING_UNITS.tsv` 为准。

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